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Conserved domains on  [gi|109150427|ref|NP_061909|]
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3-hydroxymethyl-3-methylglutaryl-CoA lyase, cytoplasmic isoform a [Homo sapiens]

Protein Classification

beta/alpha barrel domain-containing protein( domain architecture ID 229392)

beta/alpha barrel domain-containing protein belongs to a large superfamily with a wide variety of enzymatic functions

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
TIM super family cl21457
TIM-like beta/alpha barrel domains; A large family of domains similar to triose phosphate ...
 56-366 0e+00

TIM-like beta/alpha barrel domains; A large family of domains similar to triose phosphate isomerase (TIM) which, in general, share an eight beta/alpha closed barrel structure.


The actual alignment was detected with superfamily member PLN02746:

Pssm-ID: 473867  Cd Length: 347  Bit Score: 516.26  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427  56 SLAGTVACIHWETSQLSGLPEFVKIVEVGPRDGLQNEKVIVPTDIKIEFINRLSQTGLSVIEVTSFVSSRWVPQMADHTE 135
Cdd:PLN02746  25 SSSNEVGVAHMHNKLLKGLPKFVKIVEVGPRDGLQNEKNIVPTSVKVELIQRLVSSGLPVVEATSFVSPKWVPQLADAKD 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 136 VMKGIHQYPGVRYPVLTPNLQGFHHAVAAGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHMNIPARGYVSC 215
Cdd:PLN02746 105 VMAAVRNLEGARFPVLTPNLKGFEAAIAAGAKEVAVFASASESFSKSNINCSIEESLVRYREVALAAKKHSIPVRGYVSC 184

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 216 ALGCPYEGSITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQ 295
Cdd:PLN02746 185 VVGCPIEGPVPPSKVAYVAKELYDMGCYEISLGDTIGVGTPGTVVPMLEAVMAVVPVDKLAVHFHDTYGQALANILVSLQ 264

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 109150427 296 MGINVVDSAVSGLGGCPYAKGASGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFICKAVNKTTNSKVAQA 366
Cdd:PLN02746 265 MGISTVDSSVAGLGGCPYAKGASGNVATEDVVYMLNGLGVSTNVDLGKLMAAGDFISKHLGRPSGSKTAVA 335
 
Name Accession Description Interval E-value
PLN02746 PLN02746
hydroxymethylglutaryl-CoA lyase
 56-366 0e+00

hydroxymethylglutaryl-CoA lyase


Pssm-ID: 178347  Cd Length: 347  Bit Score: 516.26  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427  56 SLAGTVACIHWETSQLSGLPEFVKIVEVGPRDGLQNEKVIVPTDIKIEFINRLSQTGLSVIEVTSFVSSRWVPQMADHTE 135
Cdd:PLN02746  25 SSSNEVGVAHMHNKLLKGLPKFVKIVEVGPRDGLQNEKNIVPTSVKVELIQRLVSSGLPVVEATSFVSPKWVPQLADAKD 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 136 VMKGIHQYPGVRYPVLTPNLQGFHHAVAAGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHMNIPARGYVSC 215
Cdd:PLN02746 105 VMAAVRNLEGARFPVLTPNLKGFEAAIAAGAKEVAVFASASESFSKSNINCSIEESLVRYREVALAAKKHSIPVRGYVSC 184

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 216 ALGCPYEGSITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQ 295
Cdd:PLN02746 185 VVGCPIEGPVPPSKVAYVAKELYDMGCYEISLGDTIGVGTPGTVVPMLEAVMAVVPVDKLAVHFHDTYGQALANILVSLQ 264

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 109150427 296 MGINVVDSAVSGLGGCPYAKGASGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFICKAVNKTTNSKVAQA 366
Cdd:PLN02746 265 MGISTVDSSVAGLGGCPYAKGASGNVATEDVVYMLNGLGVSTNVDLGKLMAAGDFISKHLGRPSGSKTAVA 335
DRE_TIM_HMGL cd07938
3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; ...
 80-353 3.10e-179

3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; 3-hydroxy-3-methylglutaryl-CoA lyase (HMGL) catalyzes the cleavage of HMG-CoA to acetyl-CoA and acetoacetate, one of the terminal steps in ketone body generation and leucine degradation, and is a key enzyme in the pathway that supplies metabolic fuel to extrahepatic tissues. Mutations in HMGL cause a human autosomal recessive disorder called primary metabolic aciduria that affects ketogenesis and leucine catabolism and can be fatal due to an inability to tolerate hypoglycemia. HMGL has a TIM barrel domain with a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. The cleavage of HMG-CoA requires the presence of a divalent cation like Mg2+ or Mn2+, and the reaction is thought to involve general acid/base catalysis. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163676  Cd Length: 274  Bit Score: 498.07  E-value: 3.10e-179
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427  80 IVEVGPRDGLQNEKVIVPTDIKIEFINRLSQTGLSVIEVTSFVSSRWVPQMADHTEVMKGIHQYPGVRYPVLTPNLQGFH 159
Cdd:cd07938    1 IVEVGPRDGLQNEKTFIPTEDKIELIDALSAAGLRRIEVTSFVSPKWVPQMADAEEVLAGLPRRPGVRYSALVPNLRGAE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 160 HAVAAGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHMNIPARGYVSCALGCPYEGSITPQKVTEVSKRLYG 239
Cdd:cd07938   81 RALAAGVDEVAVFVSASETFSQKNINCSIAESLERFEPVAELAKAAGLRVRGYVSTAFGCPYEGEVPPERVAEVAERLLD 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 240 MGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQMGINVVDSAVSGLGGCPYAKGASG 319
Cdd:cd07938  161 LGCDEISLGDTIGVATPAQVRRLLEAVLERFPDEKLALHFHDTRGQALANILAALEAGVRRFDSSVGGLGGCPFAPGATG 240

                        250       260       270
                 ....*....|....*....|....*....|....
gi 109150427 320 NVATEDLIYMLNGLGLNTGVNLYKVMEAGDFICK 353
Cdd:cd07938  241 NVATEDLVYMLEGMGIETGIDLDKLLAAARWISE 274
HMGL-like pfam00682
HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and ...
 78-351 2.47e-70

HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and a region of pyruvate carboxylase.


Pssm-ID: 459902 [Multi-domain]  Cd Length: 264  Bit Score: 221.06  E-value: 2.47e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427   78 VKIVEVGPRDGLQNEKVIVPTDIKIEFINRLSQTGLSVIEVtsfvssrWVPQMA-DHTEVMKGIHQYPGVR--YPVLTPN 154
Cdd:pfam00682   2 VAICDTTLRDGEQALGVAFSIDEKLAIARALDAAGVDEIEV-------GFPAASeDDFEVVRAIAKVIPHAriLVLCRAR 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427  155 LQGFHHAVA----AGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHMNIpargyvSCALGCPYEGSITPQKV 230
Cdd:pfam00682  75 EHDIKAAVEalkgAGAVRVHVFIATSDLHRKYKLGKDREEVAKRAVAAVKAARSRGI------DVEFSPEDASRTDPEFL 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427  231 TEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGA-LAVHCHDTYGQALANILTALQMGINVVDSAVSGLG 309
Cdd:pfam00682 149 AEVVEAAIEAGATRINIPDTVGVLTPNEAAELISALKARVPNKAiISVHCHNDLGMAVANSLAAVEAGADRVDGTVNGIG 228

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 109150427  310 gcpyakGASGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFI 351
Cdd:pfam00682 229 ------ERAGNAALEEVAAALEGLGVDTGLDLQRLRSIANLV 264
LeuA COG0119
Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; ...
 86-360 3.40e-15

Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; Isopropylmalate/homocitrate/citramalate synthases is part of the Pathway/BioSystem: Isoleucine, leucine, valine biosynthesis


Pssm-ID: 439889 [Multi-domain]  Cd Length: 452  Bit Score: 76.36  E-value: 3.40e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427  86 RDGLQNEKVIVPTDIKIEFINRLSQTGLSVIEVTSFVSS-------RWVPQMADHTEVMkgihqypgvrypVLT------ 152
Cdd:COG0119   12 RDGEQAPGVSFSVEEKLRIARLLDELGVDEIEAGFPAASpgdfeavRRIAELGLDATIC------------ALArarrkd 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 153 --PNLQGfhhAVAAGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARhmnipargyvscALGCPYE-----GSI 225
Cdd:COG0119   80 idAALEA---LKGAGVDRVHLFIKTSDLHVEYKLRKTREEVLEMAVEAVKYAK------------EHGLEVEfsaedATR 144

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 226 T-PQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQMGINVVDSA 304
Cdd:COG0119  145 TdPDFLLEVLEAAIEAGADRINLPDTVGGATPNEVADLIEELRERVPDVILSVHCHNDLGLAVANSLAAVEAGADQVEGT 224

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 109150427 305 VSGLGG-CpyakgasGNVATEDLI-YMLNGLGLNTGVNLYKVMEagdfICKAVNKTTN 360
Cdd:COG0119  225 INGIGErA-------GNAALEEVVmNLKLKYGVDTGIDLSKLTE----LSRLVSEITG 271
 
Name Accession Description Interval E-value
PLN02746 PLN02746
hydroxymethylglutaryl-CoA lyase
 56-366 0e+00

hydroxymethylglutaryl-CoA lyase


Pssm-ID: 178347  Cd Length: 347  Bit Score: 516.26  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427  56 SLAGTVACIHWETSQLSGLPEFVKIVEVGPRDGLQNEKVIVPTDIKIEFINRLSQTGLSVIEVTSFVSSRWVPQMADHTE 135
Cdd:PLN02746  25 SSSNEVGVAHMHNKLLKGLPKFVKIVEVGPRDGLQNEKNIVPTSVKVELIQRLVSSGLPVVEATSFVSPKWVPQLADAKD 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 136 VMKGIHQYPGVRYPVLTPNLQGFHHAVAAGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHMNIPARGYVSC 215
Cdd:PLN02746 105 VMAAVRNLEGARFPVLTPNLKGFEAAIAAGAKEVAVFASASESFSKSNINCSIEESLVRYREVALAAKKHSIPVRGYVSC 184

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 216 ALGCPYEGSITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQ 295
Cdd:PLN02746 185 VVGCPIEGPVPPSKVAYVAKELYDMGCYEISLGDTIGVGTPGTVVPMLEAVMAVVPVDKLAVHFHDTYGQALANILVSLQ 264

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 109150427 296 MGINVVDSAVSGLGGCPYAKGASGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFICKAVNKTTNSKVAQA 366
Cdd:PLN02746 265 MGISTVDSSVAGLGGCPYAKGASGNVATEDVVYMLNGLGVSTNVDLGKLMAAGDFISKHLGRPSGSKTAVA 335
PRK05692 PRK05692
hydroxymethylglutaryl-CoA lyase; Provisional
 74-359 1.95e-179

hydroxymethylglutaryl-CoA lyase; Provisional


Pssm-ID: 180206  Cd Length: 287  Bit Score: 499.03  E-value: 1.95e-179
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427  74 LPEFVKIVEVGPRDGLQNEKVIVPTDIKIEFINRLSQTGLSVIEVTSFVSSRWVPQMADHTEVMKGIHQYPGVRYPVLTP 153
Cdd:PRK05692   1 LPKRVKIVEVGPRDGLQNEKRFIPTADKIALIDRLSAAGLSYIEVASFVSPKWVPQMADAAEVMAGIQRRPGVTYAALTP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 154 NLQGFHHAVAAGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHMNIPARGYVSCALGCPYEGSITPQKVTEV 233
Cdd:PRK05692  81 NLKGLEAALAAGADEVAVFASASEAFSQKNINCSIAESLERFEPVAEAAKQAGVRVRGYVSCVLGCPYEGEVPPEAVADV 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 234 SKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQMGINVVDSAVSGLGGCPY 313
Cdd:PRK05692 161 AERLFALGCYEISLGDTIGVGTPGQVRAVLEAVLAEFPAERLAGHFHDTYGQALANIYASLEEGITVFDASVGGLGGCPY 240

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 109150427 314 AKGASGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFICKAVNKTT 359
Cdd:PRK05692 241 APGASGNVATEDVLYMLHGLGIETGIDLDKLVRAGQFIQSKLGRPL 286
DRE_TIM_HMGL cd07938
3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; ...
 80-353 3.10e-179

3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; 3-hydroxy-3-methylglutaryl-CoA lyase (HMGL) catalyzes the cleavage of HMG-CoA to acetyl-CoA and acetoacetate, one of the terminal steps in ketone body generation and leucine degradation, and is a key enzyme in the pathway that supplies metabolic fuel to extrahepatic tissues. Mutations in HMGL cause a human autosomal recessive disorder called primary metabolic aciduria that affects ketogenesis and leucine catabolism and can be fatal due to an inability to tolerate hypoglycemia. HMGL has a TIM barrel domain with a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. The cleavage of HMG-CoA requires the presence of a divalent cation like Mg2+ or Mn2+, and the reaction is thought to involve general acid/base catalysis. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163676  Cd Length: 274  Bit Score: 498.07  E-value: 3.10e-179
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427  80 IVEVGPRDGLQNEKVIVPTDIKIEFINRLSQTGLSVIEVTSFVSSRWVPQMADHTEVMKGIHQYPGVRYPVLTPNLQGFH 159
Cdd:cd07938    1 IVEVGPRDGLQNEKTFIPTEDKIELIDALSAAGLRRIEVTSFVSPKWVPQMADAEEVLAGLPRRPGVRYSALVPNLRGAE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 160 HAVAAGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHMNIPARGYVSCALGCPYEGSITPQKVTEVSKRLYG 239
Cdd:cd07938   81 RALAAGVDEVAVFVSASETFSQKNINCSIAESLERFEPVAELAKAAGLRVRGYVSTAFGCPYEGEVPPERVAEVAERLLD 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 240 MGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQMGINVVDSAVSGLGGCPYAKGASG 319
Cdd:cd07938  161 LGCDEISLGDTIGVATPAQVRRLLEAVLERFPDEKLALHFHDTRGQALANILAALEAGVRRFDSSVGGLGGCPFAPGATG 240

                        250       260       270
                 ....*....|....*....|....*....|....
gi 109150427 320 NVATEDLIYMLNGLGLNTGVNLYKVMEAGDFICK 353
Cdd:cd07938  241 NVATEDLVYMLEGMGIETGIDLDKLLAAARWISE 274
DRE_TIM_metallolyase cd03174
DRE-TIM metallolyase superfamily; The DRE-TIM metallolyase superfamily includes ...
 81-353 1.60e-108

DRE-TIM metallolyase superfamily; The DRE-TIM metallolyase superfamily includes 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163674 [Multi-domain]  Cd Length: 265  Bit Score: 318.63  E-value: 1.60e-108
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427  81 VEVGPRDGLQNEKVIVPTDIKIEFINRLSQTGLSVIEVTSFVSSRWVPQMADHTEVMKGIHQY-PGVRYPVLTPN-LQGF 158
Cdd:cd03174    1 TDTTLRDGLQSEGATFSTEDKLEIAEALDEAGVDSIEVGSGASPKAVPQMEDDWEVLRAIRKLvPNVKLQALVRNrEKGI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 159 HHAVAAGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHMNIPARGYVSCALGCPYegsiTPQKVTEVSKRLY 238
Cdd:cd03174   81 ERALEAGVDEVRIFDSASETHSRKNLNKSREEDLENAEEAIEAAKEAGLEVEGSLEDAFGCKT----DPEYVLEVAKALE 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 239 GMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQMGINVVDSAVSGLGgcpyakGAS 318
Cdd:cd03174  157 EAGADEISLKDTVGLATPEEVAELVKALREALPDVPLGLHTHNTLGLAVANSLAALEAGADRVDGSVNGLG------ERA 230

                        250       260       270
                 ....*....|....*....|....*....|....*
gi 109150427 319 GNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFICK 353
Cdd:cd03174  231 GNAATEDLVAALEGLGIDTGIDLEKLLEISRYVEE 265
HMGL-like pfam00682
HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and ...
 78-351 2.47e-70

HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and a region of pyruvate carboxylase.


Pssm-ID: 459902 [Multi-domain]  Cd Length: 264  Bit Score: 221.06  E-value: 2.47e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427   78 VKIVEVGPRDGLQNEKVIVPTDIKIEFINRLSQTGLSVIEVtsfvssrWVPQMA-DHTEVMKGIHQYPGVR--YPVLTPN 154
Cdd:pfam00682   2 VAICDTTLRDGEQALGVAFSIDEKLAIARALDAAGVDEIEV-------GFPAASeDDFEVVRAIAKVIPHAriLVLCRAR 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427  155 LQGFHHAVA----AGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHMNIpargyvSCALGCPYEGSITPQKV 230
Cdd:pfam00682  75 EHDIKAAVEalkgAGAVRVHVFIATSDLHRKYKLGKDREEVAKRAVAAVKAARSRGI------DVEFSPEDASRTDPEFL 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427  231 TEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGA-LAVHCHDTYGQALANILTALQMGINVVDSAVSGLG 309
Cdd:pfam00682 149 AEVVEAAIEAGATRINIPDTVGVLTPNEAAELISALKARVPNKAiISVHCHNDLGMAVANSLAAVEAGADRVDGTVNGIG 228

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 109150427  310 gcpyakGASGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFI 351
Cdd:pfam00682 229 ------ERAGNAALEEVAAALEGLGVDTGLDLQRLRSIANLV 264
LeuA COG0119
Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; ...
 86-360 3.40e-15

Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; Isopropylmalate/homocitrate/citramalate synthases is part of the Pathway/BioSystem: Isoleucine, leucine, valine biosynthesis


Pssm-ID: 439889 [Multi-domain]  Cd Length: 452  Bit Score: 76.36  E-value: 3.40e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427  86 RDGLQNEKVIVPTDIKIEFINRLSQTGLSVIEVTSFVSS-------RWVPQMADHTEVMkgihqypgvrypVLT------ 152
Cdd:COG0119   12 RDGEQAPGVSFSVEEKLRIARLLDELGVDEIEAGFPAASpgdfeavRRIAELGLDATIC------------ALArarrkd 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 153 --PNLQGfhhAVAAGATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARhmnipargyvscALGCPYE-----GSI 225
Cdd:COG0119   80 idAALEA---LKGAGVDRVHLFIKTSDLHVEYKLRKTREEVLEMAVEAVKYAK------------EHGLEVEfsaedATR 144

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 226 T-PQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQMGINVVDSA 304
Cdd:COG0119  145 TdPDFLLEVLEAAIEAGADRINLPDTVGGATPNEVADLIEELRERVPDVILSVHCHNDLGLAVANSLAAVEAGADQVEGT 224

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 109150427 305 VSGLGG-CpyakgasGNVATEDLI-YMLNGLGLNTGVNLYKVMEagdfICKAVNKTTN 360
Cdd:COG0119  225 INGIGErA-------GNAALEEVVmNLKLKYGVDTGIDLSKLTE----LSRLVSEITG 271
DRE_TIM_HOA cd07943
4-hydroxy-2-oxovalerate aldolase, N-terminal catalytic TIM barrel domain; 4-hydroxy ...
 225-351 4.29e-15

4-hydroxy-2-oxovalerate aldolase, N-terminal catalytic TIM barrel domain; 4-hydroxy 2-ketovalerate aldolase (Also known as 4-hydroxy-2-ketovalerate aldolase and 4-hydroxy-2-oxopentanoate aldolase (HOA)) converts 4-hydroxy-2-oxopentanoate to acetaldehyde and pyruvate, the penultimate step in the meta-cleavage pathway for the degradation of phenols, cresols and catechol. This family includes the Escherichia coli MhpE aldolase, the Pseudomonas DmpG aldolase, and the Burkholderia xenovorans BphI pyruvate aldolase. In Pseudomonas, the DmpG aldolase tightly associates with a dehydrogenase (DmpF ) and is inactive without it. HOA has a canonical TIM-barrel fold with a C-terminal extension that forms a funnel leading to the active site. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163681  Cd Length: 263  Bit Score: 74.46  E-value: 4.29e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 225 ITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQMGINVVDSA 304
Cdd:cd07943  138 ASPEELAEQAKLMESYGADCVYVTDSAGAMLPDDVRERVRALREALDPTPVGFHGHNNLGLAVANSLAAVEAGATRIDGS 217

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 109150427 305 VSGLGGCpyakgaSGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFI 351
Cdd:cd07943  218 LAGLGAG------AGNTPLEVLVAVLERMGIETGIDLYKLMDAAEDL 258
DRE_TIM_HOA_like cd07944
4-hydroxy-2-oxovalerate aldolase-like, N-terminal catalytic TIM barrel domain; This family of ...
 194-347 4.07e-14

4-hydroxy-2-oxovalerate aldolase-like, N-terminal catalytic TIM barrel domain; This family of bacterial enzymes is sequence-similar to 4-hydroxy-2-oxovalerate aldolase (HOA) but its exact function is unknown. This family includes the Bacteroides vulgatus Bvu_2661 protein and belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163682  Cd Length: 266  Bit Score: 71.44  E-value: 4.07e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 194 KFEEVVKSARHmnIPARGY-VSCALgcPYEGSITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPP 272
Cdd:cd07944  107 EFDEALPLIKA--IKEKGYeVFFNL--MAISGYSDEELLELLELVNEIKPDVFYIVDSFGSMYPEDIKRIISLLRSNLDK 182

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 109150427 273 G-ALAVHCHDTYGQALANILTALQMGINVVDSAVSGLGgcpyaKGAsGNVATEDLIYMLNGLgLNTGVNLYKVMEA 347
Cdd:cd07944  183 DiKLGFHAHNNLQLALANTLEAIELGVEIIDATVYGMG-----RGA-GNLPTELLLDYLNNK-FGKKYNLEPVLEL 251
DRE_TIM_PC_TC_5S cd07937
Pyruvate carboxylase and Transcarboxylase 5S, carboxyltransferase domain; This family includes ...
 226-357 1.55e-13

Pyruvate carboxylase and Transcarboxylase 5S, carboxyltransferase domain; This family includes the carboxyltransferase domains of pyruvate carboxylase (PC) and the transcarboxylase (TC) 5S subunit. Transcarboxylase 5S is a cobalt-dependent metalloenzyme subunit of the biotin-dependent transcarboxylase multienzyme complex. Transcarboxylase 5S transfers carbon dioxide from the 1.3S biotin to pyruvate in the second of two carboxylation reactions catalyzed by TC. The first reaction involves the transfer of carbon dioxide from methylmalonyl-CoA to the 1.3S biotin, and is catalyzed by the 12S subunit. These two steps allow a carboxylate group to be transferred from oxaloacetate to propionyl-CoA to yield pyruvate and methylmalonyl-CoA. The catalytic domain of transcarboxylase 5S has a canonical TIM-barrel fold with a large C-terminal extension that forms a funnel leading to the active site. Transcarboxylase 5S forms a homodimer and there are six dimers per complex. In addition to the catalytic domain, transcarboxylase 5S has several other domains including a carbamoyl-phosphate synthase domain, a biotin carboxylase domain, a carboxyltransferase domain, and an ATP-grasp domain. Pyruvate carboxylase, like TC, is a biotin-dependent enzyme that catalyzes the carboxylation of pyruvate to produce oxaloacetate. In mammals, PC has critical roles in gluconeogenesis, lipogenesis, glyceroneogenesis, and insulin secretion. Inherited PC deficiencies are linked to serious diseases in humans such as lactic acidemia, hypoglycemia, psychomotor retardation, and death. PC is a single-chain enzyme and is active only in its homotetrameric form. PC has three domains, an N-terminal biotin carboxylase domain, a carboxyltransferase domain (this alignment model), and a C-terminal biotin-carboxyl carrier protein domain. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163675  Cd Length: 275  Bit Score: 70.15  E-value: 1.55e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 226 TPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIP-PgaLAVHCHDTYGQALANILTALQMGINVVDSA 304
Cdd:cd07937  147 TLEYYVKLAKELEDMGADSICIKDMAGLLTPYAAYELVKALKKEVGlP--IHLHTHDTSGLAVATYLAAAEAGVDIVDTA 224

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 109150427 305 VSGLGGCpyakgaSGNVATEDLIYMLNGLGLNTGVNLYKVMEAGDfICKAVNK 357
Cdd:cd07937  225 ISPLSGG------TSQPSTESMVAALRGTGRDTGLDLEKLEEISE-YFEEVRK 270
DRE_TIM_IPMS cd07940
2-isopropylmalate synthase (IPMS), N-terminal catalytic TIM barrel domain; 2-isopropylmalate ...
 241-353 3.18e-12

2-isopropylmalate synthase (IPMS), N-terminal catalytic TIM barrel domain; 2-isopropylmalate synthase (IPMS) catalyzes an aldol-type condensation of acetyl-CoA and 2-oxoisovalerate yielding 2-isopropylmalate and CoA, the first committed step in leucine biosynthesis. This family includes the Arabidopsis thaliana IPMS1 and IPMS2 proteins, the Glycine max GmN56 protein, and the Brassica insularis BatIMS protein. This family also includes a group of archeal IPMS-like proteins represented by the Methanocaldococcus jannaschii AksA protein. AksA catalyzes the condensation of alpha-ketoglutarate and acetyl-CoA to form trans-homoaconitate, one of 13 steps in the conversion of alpha-ketoglutarate and acetylCoA to alpha-ketosuberate, a precursor to coenzyme B and biotin. AksA also catalyzes the condensation of alpha-ketoadipate or alpha-ketopimelate with acetylCoA to form, respectively, the (R)-homocitrate homologs (R)-2-hydroxy-1,2,5-pentanetricarboxylic acid and (R)-2-hydroxy-1,2,6- hexanetricarboxylic acid. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163678  Cd Length: 268  Bit Score: 65.93  E-value: 3.18e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 241 GCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGA--LAVHCHDTYGQALANILTALQMGINVVDSAVSGLGgcpyakGAS 318
Cdd:cd07940  156 GATTINIPDTVGYLTPEEFGELIKKLKENVPNIKvpISVHCHNDLGLAVANSLAAVEAGARQVECTINGIG------ERA 229

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 109150427 319 GNVATEDLI----YMLNGLGLNTGVNLYKVMEAGDFICK 353
Cdd:cd07940  230 GNAALEEVVmalkTRYDYYGVETGIDTEELYETSRLVSR 268
PRK09282 PRK09282
pyruvate carboxylase subunit B; Validated
 226-357 2.07e-11

pyruvate carboxylase subunit B; Validated


Pssm-ID: 236449 [Multi-domain]  Cd Length: 592  Bit Score: 65.25  E-value: 2.07e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 226 TPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRmLESVMKE---IPpgaLAVHCHDTYGQALANILTALQMGINVVD 302
Cdd:PRK09282 152 TIEKYVELAKELEEMGCDSICIKDMAGLLTPYAAYE-LVKALKEevdLP---VQLHSHCTSGLAPMTYLKAVEAGVDIID 227

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 109150427 303 SAVSglggcPYAKGASgNVATEDLIYMLNGLGLNTGVNLYKVMEAGDfICKAVNK 357
Cdd:PRK09282 228 TAIS-----PLAFGTS-QPPTESMVAALKGTPYDTGLDLELLFEIAE-YFREVRK 275
PRK08195 PRK08195
4-hyroxy-2-oxovalerate/4-hydroxy-2-oxopentanoic acid aldolase,; Validated
 225-349 1.03e-10

4-hyroxy-2-oxovalerate/4-hydroxy-2-oxopentanoic acid aldolase,; Validated


Pssm-ID: 181282 [Multi-domain]  Cd Length: 337  Bit Score: 62.16  E-value: 1.03e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 225 ITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGA-LAVHCHDTYGQALANILTALQMGINVVDS 303
Cdd:PRK08195 141 APPEKLAEQAKLMESYGAQCVYVVDSAGALLPEDVRDRVRALRAALKPDTqVGFHGHNNLGLGVANSLAAVEAGATRIDG 220

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 109150427 304 AVSGLGGcpyakGAsGNVATEDLIYMLNGLGLNTGVNLYKVMEAGD 349
Cdd:PRK08195 221 SLAGLGA-----GA-GNTPLEVLVAVLDRMGWETGVDLYKLMDAAE 260
aksA PRK11858
trans-homoaconitate synthase; Reviewed
 240-364 2.59e-10

trans-homoaconitate synthase; Reviewed


Pssm-ID: 183341 [Multi-domain]  Cd Length: 378  Bit Score: 61.34  E-value: 2.59e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 240 MGCYEISLGDTIGVGTPGSM----KRMLESVMKEIppgalAVHCHDTYGQALANILTALQMGINVVDSAVSGLGgcpyak 315
Cdd:PRK11858 157 AGADRVRFCDTVGILDPFTMyelvKELVEAVDIPI-----EVHCHNDFGMATANALAGIEAGAKQVHTTVNGLG------ 225

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 109150427 316 GASGNVATEDLIYMLNGL-GLNTGVNLYKVMEagdfICKAVNKTTNSKVA 364
Cdd:PRK11858 226 ERAGNAALEEVVMALKYLyGIDLGIDTERLYE----LSRLVSKASGIPVP 271
PRK14040 PRK14040
oxaloacetate decarboxylase subunit alpha;
195-346 4.56e-10

oxaloacetate decarboxylase subunit alpha;


Pssm-ID: 237592 [Multi-domain]  Cd Length: 593  Bit Score: 61.10  E-value: 4.56e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 195 FEEVVKSARHMNIPARGYVScalgcpYEGSI--TPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGS----MKRMLESVmk 268
Cdd:PRK14040 126 LETALKAVRKVGAHAQGTLS------YTTSPvhTLQTWVDLAKQLEDMGVDSLCIKDMAGLLKPYAayelVSRIKKRV-- 197

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 109150427 269 EIPpgaLAVHCHDTYGQALANILTALQMGINVVDSAVSGLgGCPYakgasGNVATEDLIYMLNGLGLNTGVNLYKVME 346
Cdd:PRK14040 198 DVP---LHLHCHATTGLSTATLLKAIEAGIDGVDTAISSM-SMTY-----GHSATETLVATLEGTERDTGLDILKLEE 266
PRK12330 PRK12330
methylmalonyl-CoA carboxytransferase subunit 5S;
226-349 4.85e-10

methylmalonyl-CoA carboxytransferase subunit 5S;


Pssm-ID: 183445 [Multi-domain]  Cd Length: 499  Bit Score: 60.93  E-value: 4.85e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 226 TPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGA-LAVHCHDTYGQALANILTALQMGINVVDSA 304
Cdd:PRK12330 153 TVEGFVEQAKRLLDMGADSICIKDMAALLKPQPAYDIVKGIKEACGEDTrINLHCHSTTGVTLVSLMKAIEAGVDVVDTA 232

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 109150427 305 VSGLGGCPyakgasGNVATEDLIYMLNGLGLNTGVNLYKVMEAGD 349
Cdd:PRK12330 233 ISSMSLGP------GHNPTESLVEMLEGTGYTTKLDMDRLLKIRD 271
PRK12331 PRK12331
oxaloacetate decarboxylase subunit alpha;
232-350 5.95e-10

oxaloacetate decarboxylase subunit alpha;


Pssm-ID: 183446 [Multi-domain]  Cd Length: 448  Bit Score: 60.49  E-value: 5.95e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 232 EVSKRLYGMGCYEISLGDTIGVGTPGS----MKRMLESVmkEIPpgaLAVHCHDTYGQALANILTALQMGINVVDSAVSg 307
Cdd:PRK12331 158 KLAKEMQEMGADSICIKDMAGILTPYVayelVKRIKEAV--TVP---LEVHTHATSGIAEMTYLKAIEAGADIIDTAIS- 231

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 109150427 308 lggcPYAKGASgNVATEDLIYMLNGLGLNTGVNLYKVMEAGDF 350
Cdd:PRK12331 232 ----PFAGGTS-QPATESMVAALQDLGYDTGLDLEELSEIAEY 269
DRE_TIM_HCS cd07948
Saccharomyces cerevisiae homocitrate synthase and related proteins, catalytic TIM barrel ...
 78-309 1.01e-09

Saccharomyces cerevisiae homocitrate synthase and related proteins, catalytic TIM barrel domain; Homocitrate synthase (HCS) catalyzes the condensation of acetyl-CoA and alpha-ketoglutarate to form homocitrate, the first step in the lysine biosynthesis pathway. This family includes the Yarrowia lipolytica LYS1 protein as well as the Saccharomyces cerevisiae LYS20 and LYS21 proteins. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163685  Cd Length: 262  Bit Score: 58.50  E-value: 1.01e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427  78 VKIVEVGPRDGLQNEKVIVPTDIKIEFINRLSQTGLSVIEVTSFVSSrwvPQMADHTEVMKGIhqypGVRYPVLTP---N 154
Cdd:cd07948    1 FKIIDSTLREGEQFANAFFDTEDKIEIAKALDAFGVDYIELTSPAAS---PQSRADCEAIAKL----GLKAKILTHircH 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 155 LQGFHHAVAAGATEISVFGAASE---SFSK-KNINCSIEESMgkfeEVVKSARHMNIPARgyVSCalgcpyEGSITpqkv 230
Cdd:cd07948   74 MDDARIAVETGVDGVDLVFGTSPflrEASHgKSITEIIESAV----EVIEFVKSKGIEVR--FSS------EDSFR---- 137

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 231 TEVSK--RLYG----MGCYEISLGDTIGVGTPGSMKRMLESVMKEIPPGaLAVHCHDTYGQALANILTALQMGINVVDSA 304
Cdd:cd07948  138 SDLVDllRVYRavdkLGVNRVGIADTVGIATPRQVYELVRTLRGVVSCD-IEFHGHNDTGCAIANAYAALEAGATHIDTT 216


                 ....*
gi 109150427 305 VSGLG 309
Cdd:cd07948  217 VLGIG 221
PRK09389 PRK09389
(R)-citramalate synthase; Provisional
 235-364 3.92e-09

(R)-citramalate synthase; Provisional


Pssm-ID: 236493 [Multi-domain]  Cd Length: 488  Bit Score: 58.03  E-value: 3.92e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 235 KRLYGMGcyeISLG-------DTIGVGTPgsmKRMLESV--MKEIPPGALAVHCHDTYGQALANILTALQMGINVVDSAV 305
Cdd:PRK09389 146 KELYKAG---IEAGadricfcDTVGILTP---EKTYELFkrLSELVKGPVSIHCHNDFGLAVANTLAALAAGADQVHVTI 219

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 306 SGLGgcpyakGASGNVATEDLIYMLNGL-GLNTGVNLYKVMEagdfICKAVNKTTNSKVA 364
Cdd:PRK09389 220 NGIG------ERAGNASLEEVVMALKHLyDVETGIKLEELYE----LSRLVSRLTGIPVP 269
PRK00915 PRK00915
2-isopropylmalate synthase; Validated
 195-363 7.07e-09

2-isopropylmalate synthase; Validated


Pssm-ID: 234864 [Multi-domain]  Cd Length: 513  Bit Score: 57.04  E-value: 7.07e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 195 FEEVVKSARHMNIPARGYV-----SCalgcpyE-GSIT-PQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVM 267
Cdd:PRK00915 115 REEVLEMAVEAVKYARSYTddvefSA------EdATRTdLDFLCRVVEAAIDAGATTINIPDTVGYTTPEEFGELIKTLR 188

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 268 KEIPPGALA---VHCHDTYGQALANILTALQMGINVVDSAVSGLGgcpyaKGAsGNVATEDLIYMLN----GLGLNTGVN 340
Cdd:PRK00915 189 ERVPNIDKAiisVHCHNDLGLAVANSLAAVEAGARQVECTINGIG-----ERA-GNAALEEVVMALKtrkdIYGVETGIN 262

                        170       180
                 ....*....|....*....|...
gi 109150427 341 LYKVMEAgdfiCKAVNKTTNSKV 363
Cdd:PRK00915 263 TEEIYRT----SRLVSQLTGMPV 281
PLN03228 PLN03228
methylthioalkylmalate synthase; Provisional
 77-345 2.75e-08

methylthioalkylmalate synthase; Provisional


Pssm-ID: 178767 [Multi-domain]  Cd Length: 503  Bit Score: 55.31  E-value: 2.75e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427  77 FVKIVEVGPRDGLQNEKVIVPTDIKIEFINRLSQTGLSVIEVTSFVSSRwvpqmaDHTEVMKGIHQYPGVR-------YP 149
Cdd:PLN03228  84 YVRVLDTTLRDGEQSPGGSLTPPQKLEIARQLAKLRVDIMEVGFPGSSE------EEFEAVKTIAKTVGNEvdeetgyVP 157

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 150 VLTPNLQGFHHAVAAG--------ATEISVFGAASESFSKKNINCSIEESMGKFEEVVKSARHMniparGYVSCALGCPY 221
Cdd:PLN03228 158 VICGIARCKKRDIEAAwealkyakRPRILAFTSTSDIHMKYKLKKTKEEVIEMAVSSIRYAKSL-----GFHDIQFGCED 232

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 222 EGSITPQKVTEVSKRLYGMGCYEISLGDTIGVGTPGSMKRMLESVmKEIPPGA----LAVHCHDTYGQALANILTALQMG 297
Cdd:PLN03228 233 GGRSDKEFLCKILGEAIKAGATSVGIADTVGINMPHEFGELVTYV-KANTPGIddivFSVHCHNDLGLATANTIAGICAG 311

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 109150427 298 INVVDSAVSGLGgcpyakGASGNVATEDLI--------YMLNglGLNTGVNLYKVM 345
Cdd:PLN03228 312 ARQVEVTINGIG------ERSGNASLEEVVmalkcrgaYLMN--GVYTGIDTRQIM 359
DRE_TIM_CMS cd07945
Leptospira interrogans citramalate synthase (CMS) and related proteins, N-terminal catalytic ...
 245-340 3.69e-06

Leptospira interrogans citramalate synthase (CMS) and related proteins, N-terminal catalytic TIM barrel domain; Citramalate synthase (CMS) catalyzes the conversion of pyruvate and acetyl-CoA to (R)-citramalate in the first dedicated step of the citramalate pathway. Citramalate is only found in Leptospira interrogans and a few other microorganisms. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163683 [Multi-domain]  Cd Length: 280  Bit Score: 48.14  E-value: 3.69e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 245 ISLGDTIGVGTPGSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQMGINVVDSAVSGLGgcpyakGASGNVATE 324
Cdd:cd07945  164 IMLPDTLGILSPFETYTYISDMVKRYPNLHFDFHAHNDYDLAVANVLAAVKAGIKGLHTTVNGLG------ERAGNAPLA 237

                         90
                 ....*....|....*..
gi 109150427 325 DLIYMLNG-LGLNTGVN 340
Cdd:cd07945  238 SVIAVLKDkLKVKTNID 254
DRE_TIM_Re_CS cd07947
Clostridium kluyveri Re-citrate synthase and related proteins, catalytic TIM barrel domain; ...
 181-351 4.21e-06

Clostridium kluyveri Re-citrate synthase and related proteins, catalytic TIM barrel domain; Re-citrate synthase (Re-CS) is a Clostridium kluyveri enzyme that converts acetyl-CoA and oxaloacetate to citrate. In most organisms, this reaction is catalyzed by Si-citrate synthase which is Si-face stereospecific with respect to C-2 of oxaloacetate, and phylogenetically unrelated to Re-citrate synthase. Re-citrate synthase is also found in a few other strictly anaerobic organisms. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163684  Cd Length: 279  Bit Score: 47.70  E-value: 4.21e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 181 KKNINCSIEESMGKFEEVVKSARHMNIPARgyvsCALG----CPYEGSITP--QKVTEVSKRlYGMGCYeISLGDTIGVG 254
Cdd:cd07947  103 FKKLKMTREEAMEKYLEIVEEALDHGIKPR----CHLEditrADIYGFVLPfvNKLMKLSKE-SGIPVK-IRLCDTLGYG 176

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 255 T-------PGSMKRMLESVMKE--IPPGALAVHCHDTYGQALANILTALQMGINVVDSAVSGLGgcpyakGASGNVATED 325
Cdd:cd07947  177 VpypgaslPRSVPKIIYGLRKDcgVPSENLEWHGHNDFYKAVANAVAAWLYGASWVNCTLLGIG------ERTGNCPLEA 250

                        170       180
                 ....*....|....*....|....*..
gi 109150427 326 LIYMLNGLGLNT-GVNLYKVMEAGDFI 351
Cdd:cd07947  251 MVIEYAQLKGNFdGMNLEVITEIAEYF 277
DRE_TIM_LeuA3 cd07941
Desulfobacterium autotrophicum LeuA3 and related proteins, N-terminal catalytic TIM barrel ...
 245-309 8.08e-06

Desulfobacterium autotrophicum LeuA3 and related proteins, N-terminal catalytic TIM barrel domain; Desulfobacterium autotrophicum LeuA3 is sequence-similar to alpha-isopropylmalate synthase (LeuA) but its exact function is unknown. Members of this family have an N-terminal TIM barrel domain that belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163679  Cd Length: 273  Bit Score: 46.68  E-value: 8.08e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 109150427 245 ISLGDTIGvGT-PGSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQMGINVVDSAVSGLG 309
Cdd:cd07941  168 LVLCDTNG-GTlPHEIAEIVKEVRERLPGVPLGIHAHNDSGLAVANSLAAVEAGATQVQGTINGYG 232
PRK14042 PRK14042
pyruvate carboxylase subunit B; Provisional
 232-357 1.10e-05

pyruvate carboxylase subunit B; Provisional


Pssm-ID: 172536 [Multi-domain]  Cd Length: 596  Bit Score: 47.41  E-value: 1.10e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 232 EVSKRLYGMGCYEISLGDTIGVGTPgSMKRMLESVMKEIPPGALAVHCHDTYGQALANILTALQMGINVVDSAVSGLGGc 311
Cdd:PRK14042 158 ELGKKLAEMGCDSIAIKDMAGLLTP-TVTVELYAGLKQATGLPVHLHSHSTSGLASICHYEAVLAGCNHIDTAISSFSG- 235

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 109150427 312 pyakGASgNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFIcKAVNK 357
Cdd:PRK14042 236 ----GAS-HPPTEALVAALTDTPYDTELDLNILLEIDDYF-KAVRK 275
PRK12581 PRK12581
oxaloacetate decarboxylase; Provisional
 235-357 1.89e-05

oxaloacetate decarboxylase; Provisional


Pssm-ID: 79056 [Multi-domain]  Cd Length: 468  Bit Score: 46.26  E-value: 1.89e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427 235 KRLYGMGCYEISLGDTIGVGTPGSMKRMLESV--MKEIPpgaLAVHCHDTYGQALANILTALQMGINVVDSAVSglggcP 312
Cdd:PRK12581 170 KELVEMGADSICIKDMAGILTPKAAKELVSGIkaMTNLP---LIVHTHATSGISQMTYLAAVEAGADRIDTALS-----P 241

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 109150427 313 YAKGASgNVATEDLIYMLNGLGLNTGVNLYKVMEAGDFICKAVNK 357
Cdd:PRK12581 242 FSEGTS-QPATESMYLALKEAGYDITLDETLLEQAANHLRQARQK 285
DRE_TIM_NifV cd07939
Streptomyces rubellomurinus FrbC and related proteins, catalytic TIM barrel domain; FrbC (NifV) ...
 249-309 3.64e-05

Streptomyces rubellomurinus FrbC and related proteins, catalytic TIM barrel domain; FrbC (NifV) of Streptomyces rubellomurinus catalyzes the condensation of acetyl-CoA and alpha-ketoglutarate to form homocitrate and CoA, a reaction similar to one catalyzed by homocitrate synthase. The gene encoding FrbC is one of several genes required for the biosynthesis of FR900098, a potent antimalarial antibiotic. This protein is also required for assembly of the nitrogenase MoFe complex but its exact role is unknown. This family also includes the NifV proteins of Heliobacterium chlorum and Gluconacetobacter diazotrophicus, which appear to be orthologous to FrbC. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163677 [Multi-domain]  Cd Length: 259  Bit Score: 44.80  E-value: 3.64e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 109150427 249 DTIGVGTPGSMKRMLESVMKEIPpGALAVHCHDTYGQALANILTALQMGINVVDSAVSGLG 309
Cdd:cd07939  160 DTVGILDPFTTYELIRRLRAATD-LPLEFHAHNDLGLATANTLAAVRAGATHVSVTVNGLG 219
PRK12999 PRK12999
pyruvate carboxylase; Reviewed
 277-355 2.57e-03

pyruvate carboxylase; Reviewed


Pssm-ID: 237263 [Multi-domain]  Cd Length: 1146  Bit Score: 40.12  E-value: 2.57e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150427  277 VHCHDTYGQALANILTALQMGINVVDSAVSGLGGcpyakGAS-GNVATedLIYMLNGLGLNTGVNLYKVMEAGDFiCKAV 355
Cdd:PRK12999  739 LHTHDTSGNGLATYLAAAEAGVDIVDVAVASMSG-----LTSqPSLNS--IVAALEGTERDTGLDLDAIRKLSPY-WEAV 810
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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