NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|159341089|ref|YP_001542648|]
View 

thymidylate synthase [Acidianus rod-shaped virus 1]

Protein Classification

FAD-dependent thymidylate synthase( domain architecture ID 10003577)

FAD-dependent thymidylate synthase catalyzes the formation of dTMP and tetrahydrofolate from dUMP and methylenetetrahydrofolate using a flavin coenzyme as the source of reducing equivalents, derived from NADPH

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
ThyX COG1351
Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; ...
 4-198 3.95e-89

Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; Thymidylate synthase ThyX, FAD-dependent family is part of the Pathway/BioSystem: Thymidylate biosynthesis


:

Pssm-ID: 440962  Cd Length: 197  Bit Score: 261.77  E-value: 3.95e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159341089   4 VSLVSYTQNGEKVVAIASKMSRSRKGWKHHEETMTEDEIETWIRDAIIHGYWSPLEHSNYTFSIEGISRVASHQLVRHRI 83
Cdd:COG1351    3 VRLIDYTPDPEDLIAAAARVSYSSKSLRELLKELSEEKAEKLIRRLLRHGHESPFEHASFTFAIEGVSRAVTHQLVRHRI 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159341089  84 ASYTQMSHRFAKPIDEYYqpIIPPSAEKRNE--EIIKNAYKDAYDLYYDLLQNGVPEEDARYILPNGVNTNIVVTMNARE 161
Cdd:COG1351   83 ASYSQQSQRYVKLDDKEY--YIPPEIAKNEEllEEYEEAMEKAFEAYEELLERGVAREDARYVLPNATETKIVVTMNLRE 160

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 159341089 162 LYNFFGLRLCSRAQWEIRAVAWKMLEEVKRVHPRLFK 198
Cdd:COG1351  161 LLHFLKLRCCSHAQWEIRELAEAMLEELKKVAPLLFE 197
 
Name Accession Description Interval E-value
ThyX COG1351
Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; ...
 4-198 3.95e-89

Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; Thymidylate synthase ThyX, FAD-dependent family is part of the Pathway/BioSystem: Thymidylate biosynthesis


Pssm-ID: 440962  Cd Length: 197  Bit Score: 261.77  E-value: 3.95e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159341089   4 VSLVSYTQNGEKVVAIASKMSRSRKGWKHHEETMTEDEIETWIRDAIIHGYWSPLEHSNYTFSIEGISRVASHQLVRHRI 83
Cdd:COG1351    3 VRLIDYTPDPEDLIAAAARVSYSSKSLRELLKELSEEKAEKLIRRLLRHGHESPFEHASFTFAIEGVSRAVTHQLVRHRI 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159341089  84 ASYTQMSHRFAKPIDEYYqpIIPPSAEKRNE--EIIKNAYKDAYDLYYDLLQNGVPEEDARYILPNGVNTNIVVTMNARE 161
Cdd:COG1351   83 ASYSQQSQRYVKLDDKEY--YIPPEIAKNEEllEEYEEAMEKAFEAYEELLERGVAREDARYVLPNATETKIVVTMNLRE 160

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 159341089 162 LYNFFGLRLCSRAQWEIRAVAWKMLEEVKRVHPRLFK 198
Cdd:COG1351  161 LLHFLKLRCCSHAQWEIRELAEAMLEELKKVAPLLFE 197
thyX TIGR02170
thymidylate synthase, flavin-dependent; Two forms of microbial thymidylate synthase are known: ...
 3-199 3.23e-78

thymidylate synthase, flavin-dependent; Two forms of microbial thymidylate synthase are known: ThyA (2.1.1.45) and ThyX (2.1.1.148). This model describes ThyX, a homotetrameric flavoprotein. Both enzymes convert dUMP to dTMP. Under oxygen-limiting conditions, thyX can complement a thyA mutation. [Purines, pyrimidines, nucleosides, and nucleotides, 2'-Deoxyribonucleotide metabolism]


Pssm-ID: 274010  Cd Length: 209  Bit Score: 234.55  E-value: 3.23e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159341089    3 SVSLVSYTQNGEKVVAIASKMSRSRKGWKHHEETMTEDeietWIRDAIIHGYWSPLEHSNYTFSIEGISRVASHQLVRHR 82
Cdd:TIGR02170   1 FVKLIDYTPGPDALIVQAARVSYSSFEKDKPGTATDAG----LIDYLLRHGHFSPLEHASFTFEVKGASRSVAAQLTRHR 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159341089   83 IASYTQMSHRFAK---PIDEYYQPIIPPSAEKRN------------EEIIKNAYKDAYDLYYDLLQNGVPEEDARYILPN 147
Cdd:TIGR02170  77 IASYSVQSQRYVLlrnEAPEGERVVVPPSVNDTNldekpeevvekaYAEAEDHYRASYELYRKLLEAGIAREDARFVLPN 156

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 159341089  148 GVNTNIVVTMNARELYNFFGLRLCSRAQWEIRAVAWKMLEEVKRVHPRLFKY 199
Cdd:TIGR02170 157 ALYTHIVVTGNARSLMHFLDLRASNDAQWEIRELAEAMLDIVKEVAPWVFEA 208
Thy1 pfam02511
Thymidylate synthase complementing protein; Thymidylate synthase complementing protein (Thy1) ...
 9-194 1.20e-75

Thymidylate synthase complementing protein; Thymidylate synthase complementing protein (Thy1) complements the thymidine growth requirement of the organizms in which it is found, but shows no homology to thymidylate synthase. The bacterial members of this family at least are flavin-dependent thymidylate synthases.


Pssm-ID: 460576  Cd Length: 186  Bit Score: 227.52  E-value: 1.20e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159341089    9 YTqNGEKVVAIASKMSRSrkgwKHHEETMTEDEIETWIRDAIIHGYWSPLEHSNYTFSIEGISRVASHQLVRHRIASYTQ 88
Cdd:pfam02511   1 YT-DPEKLIAAAARVCYG----SSSKPDELEEKDEKLIRYLLRHGHGSPFEHASFTFAIEGVSRSVARQLVRHRIASFSQ 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159341089   89 MSHRFAKPIDEYYqpIIPPSAEKRN------EEIIKNAYKDAYDLYYDLLQNGVPEEDARYILPNGVNTNIVVTMNAREL 162
Cdd:pfam02511  76 QSQRYVDLDDEEF--VIPPEIALRGaqseelDELYEEAMEEAYEAYEELLEAGVAREDARYVLPNATETRIVVTMNARSL 153

                         170       180       190
                  ....*....|....*....|....*....|..
gi 159341089  163 YNFFGLRLCSRAQWEIRAVAWKMLEEVKRVHP 194
Cdd:pfam02511 154 LHFLELRCCPRAQWEIRELAEEMLEELKKVAP 185
ThyX cd20175
FAD-dependent thymidylate synthase (ThyX), mechanistically and structurally unrelated to ...
 5-191 1.65e-65

FAD-dependent thymidylate synthase (ThyX), mechanistically and structurally unrelated to thymidylate synthase (ThyA); This family contains FAD-dependent thymidylate synthase (also known as ThyX, Thy1, FDTS or thymidylate synthase complementing protein), found in many microbial genomes including several human pathogens, but absent in humans. This protein is mechanistically and structurally unrelated to thymidylate synthase (TS or ThyA) found in mammals. ThyA and ThyX both produce de novo thymidylate or deoxythymidine 5'-monophosphate (dTMP), an essential DNA precursor. The classic ThyA catalyzes the reductive methylation of deoxyuridine 5'-monophosphate (dUMP) to form dTMP, with methylenetetrahydrofolate (CH2H4folate) serving as a one-carbon donor and as the source of reductive power. On the other hand, ThyX contains FAD, tightly bound by a novel fold, that mediates hydride transfer from NADPH during catalysis. Consequently, CH2H4folate serves only as a carbon donor and tetrahydrofolate (and not dihydrofolate as in the case of ThyA) is produced. The differences between the ThyX and ThyA is used for mechanism-based drugs to selectively inhibit FDTS and not have much effect on human and other eukaryotic TS. ThyX has been pursued for the development of new antibacterial agents against Mycobacterium tuberculosis, the causative agent of the widespread infectious disease tuberculosis (TB). It is also an attractive target for designing specific antibiotic drugs against many diseases such as ulcers, periodontal disease, and Lyme's disease, as well as biological warfare agents such as anthrax, botulism, and typhus.


Pssm-ID: 412038 [Multi-domain]  Cd Length: 186  Bit Score: 201.51  E-value: 1.65e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159341089   5 SLVSYTQNGE----KVVAIASKMSRSRKGwkhheETMTEDEIETWIRDAI-IHGYWSPLEHSNYTFSIEGISrVASHQLV 79
Cdd:cd20175    1 ELIDYTPDPEekpeELIAAAARVSYSSEG-----EEKAEEEDEKLIKRLLkRDGHGSVLEHASFTFEIEGVS-AATHQLV 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159341089  80 RHRIASYTQMSHRFAKPIDEYYQPIIPPSAEKRNEEIIKNAYKDAYDLYYDLLQNGVPEEDARYILPNGVNTNIVVTMNA 159
Cdd:cd20175   75 RHRIASFTQESQRYVDLSGFKYPPPPPEIEDEELEELYEEAMEEAEELYEKLLEAGIAKEDARYVLPNATKTRIVVTMNL 154

                        170       180       190
                 ....*....|....*....|....*....|..
gi 159341089 160 RELYNFFGLRLCSRAQWEIRAVAWKMLEEVKR 191
Cdd:cd20175  155 RELLHFLELRTCPHAQWEIRELAEEMLEELKK 186
 
Name Accession Description Interval E-value
ThyX COG1351
Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; ...
 4-198 3.95e-89

Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; Thymidylate synthase ThyX, FAD-dependent family is part of the Pathway/BioSystem: Thymidylate biosynthesis


Pssm-ID: 440962  Cd Length: 197  Bit Score: 261.77  E-value: 3.95e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159341089   4 VSLVSYTQNGEKVVAIASKMSRSRKGWKHHEETMTEDEIETWIRDAIIHGYWSPLEHSNYTFSIEGISRVASHQLVRHRI 83
Cdd:COG1351    3 VRLIDYTPDPEDLIAAAARVSYSSKSLRELLKELSEEKAEKLIRRLLRHGHESPFEHASFTFAIEGVSRAVTHQLVRHRI 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159341089  84 ASYTQMSHRFAKPIDEYYqpIIPPSAEKRNE--EIIKNAYKDAYDLYYDLLQNGVPEEDARYILPNGVNTNIVVTMNARE 161
Cdd:COG1351   83 ASYSQQSQRYVKLDDKEY--YIPPEIAKNEEllEEYEEAMEKAFEAYEELLERGVAREDARYVLPNATETKIVVTMNLRE 160

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 159341089 162 LYNFFGLRLCSRAQWEIRAVAWKMLEEVKRVHPRLFK 198
Cdd:COG1351  161 LLHFLKLRCCSHAQWEIRELAEAMLEELKKVAPLLFE 197
thyX TIGR02170
thymidylate synthase, flavin-dependent; Two forms of microbial thymidylate synthase are known: ...
 3-199 3.23e-78

thymidylate synthase, flavin-dependent; Two forms of microbial thymidylate synthase are known: ThyA (2.1.1.45) and ThyX (2.1.1.148). This model describes ThyX, a homotetrameric flavoprotein. Both enzymes convert dUMP to dTMP. Under oxygen-limiting conditions, thyX can complement a thyA mutation. [Purines, pyrimidines, nucleosides, and nucleotides, 2'-Deoxyribonucleotide metabolism]


Pssm-ID: 274010  Cd Length: 209  Bit Score: 234.55  E-value: 3.23e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159341089    3 SVSLVSYTQNGEKVVAIASKMSRSRKGWKHHEETMTEDeietWIRDAIIHGYWSPLEHSNYTFSIEGISRVASHQLVRHR 82
Cdd:TIGR02170   1 FVKLIDYTPGPDALIVQAARVSYSSFEKDKPGTATDAG----LIDYLLRHGHFSPLEHASFTFEVKGASRSVAAQLTRHR 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159341089   83 IASYTQMSHRFAK---PIDEYYQPIIPPSAEKRN------------EEIIKNAYKDAYDLYYDLLQNGVPEEDARYILPN 147
Cdd:TIGR02170  77 IASYSVQSQRYVLlrnEAPEGERVVVPPSVNDTNldekpeevvekaYAEAEDHYRASYELYRKLLEAGIAREDARFVLPN 156

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 159341089  148 GVNTNIVVTMNARELYNFFGLRLCSRAQWEIRAVAWKMLEEVKRVHPRLFKY 199
Cdd:TIGR02170 157 ALYTHIVVTGNARSLMHFLDLRASNDAQWEIRELAEAMLDIVKEVAPWVFEA 208
Thy1 pfam02511
Thymidylate synthase complementing protein; Thymidylate synthase complementing protein (Thy1) ...
 9-194 1.20e-75

Thymidylate synthase complementing protein; Thymidylate synthase complementing protein (Thy1) complements the thymidine growth requirement of the organizms in which it is found, but shows no homology to thymidylate synthase. The bacterial members of this family at least are flavin-dependent thymidylate synthases.


Pssm-ID: 460576  Cd Length: 186  Bit Score: 227.52  E-value: 1.20e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159341089    9 YTqNGEKVVAIASKMSRSrkgwKHHEETMTEDEIETWIRDAIIHGYWSPLEHSNYTFSIEGISRVASHQLVRHRIASYTQ 88
Cdd:pfam02511   1 YT-DPEKLIAAAARVCYG----SSSKPDELEEKDEKLIRYLLRHGHGSPFEHASFTFAIEGVSRSVARQLVRHRIASFSQ 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159341089   89 MSHRFAKPIDEYYqpIIPPSAEKRN------EEIIKNAYKDAYDLYYDLLQNGVPEEDARYILPNGVNTNIVVTMNAREL 162
Cdd:pfam02511  76 QSQRYVDLDDEEF--VIPPEIALRGaqseelDELYEEAMEEAYEAYEELLEAGVAREDARYVLPNATETRIVVTMNARSL 153

                         170       180       190
                  ....*....|....*....|....*....|..
gi 159341089  163 YNFFGLRLCSRAQWEIRAVAWKMLEEVKRVHP 194
Cdd:pfam02511 154 LHFLELRCCPRAQWEIRELAEEMLEELKKVAP 185
ThyX cd20175
FAD-dependent thymidylate synthase (ThyX), mechanistically and structurally unrelated to ...
 5-191 1.65e-65

FAD-dependent thymidylate synthase (ThyX), mechanistically and structurally unrelated to thymidylate synthase (ThyA); This family contains FAD-dependent thymidylate synthase (also known as ThyX, Thy1, FDTS or thymidylate synthase complementing protein), found in many microbial genomes including several human pathogens, but absent in humans. This protein is mechanistically and structurally unrelated to thymidylate synthase (TS or ThyA) found in mammals. ThyA and ThyX both produce de novo thymidylate or deoxythymidine 5'-monophosphate (dTMP), an essential DNA precursor. The classic ThyA catalyzes the reductive methylation of deoxyuridine 5'-monophosphate (dUMP) to form dTMP, with methylenetetrahydrofolate (CH2H4folate) serving as a one-carbon donor and as the source of reductive power. On the other hand, ThyX contains FAD, tightly bound by a novel fold, that mediates hydride transfer from NADPH during catalysis. Consequently, CH2H4folate serves only as a carbon donor and tetrahydrofolate (and not dihydrofolate as in the case of ThyA) is produced. The differences between the ThyX and ThyA is used for mechanism-based drugs to selectively inhibit FDTS and not have much effect on human and other eukaryotic TS. ThyX has been pursued for the development of new antibacterial agents against Mycobacterium tuberculosis, the causative agent of the widespread infectious disease tuberculosis (TB). It is also an attractive target for designing specific antibiotic drugs against many diseases such as ulcers, periodontal disease, and Lyme's disease, as well as biological warfare agents such as anthrax, botulism, and typhus.


Pssm-ID: 412038 [Multi-domain]  Cd Length: 186  Bit Score: 201.51  E-value: 1.65e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159341089   5 SLVSYTQNGE----KVVAIASKMSRSRKGwkhheETMTEDEIETWIRDAI-IHGYWSPLEHSNYTFSIEGISrVASHQLV 79
Cdd:cd20175    1 ELIDYTPDPEekpeELIAAAARVSYSSEG-----EEKAEEEDEKLIKRLLkRDGHGSVLEHASFTFEIEGVS-AATHQLV 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 159341089  80 RHRIASYTQMSHRFAKPIDEYYQPIIPPSAEKRNEEIIKNAYKDAYDLYYDLLQNGVPEEDARYILPNGVNTNIVVTMNA 159
Cdd:cd20175   75 RHRIASFTQESQRYVDLSGFKYPPPPPEIEDEELEELYEEAMEEAEELYEKLLEAGIAKEDARYVLPNATKTRIVVTMNL 154

                        170       180       190
                 ....*....|....*....|....*....|..
gi 159341089 160 RELYNFFGLRLCSRAQWEIRAVAWKMLEEVKR 191
Cdd:cd20175  155 RELLHFLELRTCPHAQWEIRELAEEMLEELKK 186
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH