1GDH,2H1S,2GCG,2DBR,2CUK


Conserved Protein Domain Family
GDH

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cd05301: GDH 
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D-glycerate dehydrogenase/hydroxypyruvate reductase (GDH)
D-glycerate dehydrogenase (GDH, also known as hydroxypyruvate reductase, HPR) catalyzes the reversible reaction of (R)-glycerate + NAD+ to hydroxypyruvate + NADH + H+. In humans, HPR deficiency causes primary hyperoxaluria type 2, characterized by over-excretion of L-glycerate and oxalate in the urine, possibly due to an imbalance in competition with L-lactate dehydrogenase, another formate dehydrogenase (FDH)-like enzyme. GDH, like FDH and other members of the D-specific hydroxyacid dehydrogenase family that also includes L-alanine dehydrogenase and S-adenosylhomocysteine hydrolase, typically have a characteristic arrangement of 2 similar subdomains of the alpha/beta Rossmann-fold NAD+ binding form, despite often low sequence identity. The NAD+ binding domain is inserted within the linear sequence of the mostly N-terminal catalytic domain, which has a similar domain structure to the internal NAD binding domain. Structurally, these domains are connected by extended alpha helices and create a cleft in which NAD is bound, primarily to the C-terminal portion of the 2nd (internal) domain. Some related proteins have similar structural subdomain but with a tandem arrangement of the catalytic and NAD-binding subdomains in the linear sequence. While many members of this family are dimeric, alanine DH is hexameric and phosphoglycerate DH is tetrameric.
Statistics
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PSSM-Id: 240626
Aligned: 168 rows
Threshold Bit Score: 324.348
Created: 26-Oct-2005
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 25 residues -Click on image for an interactive view with Cn3D
Feature 1:NADP binding site [chemical binding site]
Evidence:
  • Structure:2GCG: Human Glyoxylate reductase binds NADP, contacts at 4A
  • Structure:2DBR: Pyrococcus horikoshii Glyoxylate Reductase binds NADP; contacts at 4A
  • Comment:GxGxxG(17x)[DN] is canonical NAD binding motif
  • Citation:PMID 8053888
  • Citation:PMID 8053888

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                                     
1GDH_A      2 KKILITWPLPe-AAMARARe--sYDVIAHGdd--------pkITIDEMIetaksVDALLITLNEkCRKEVIDRIPenIKC 70  Hyphomicrobium met...
2GCG_A      9 MKVFVTRRIPa-EGRVALAraadCEVEQWDsd--------epIPAKELErgvagAHGLLCLLSDhVDKRILDAAGanLKV 79  human
NP_559036   2 PCIFVSREGFpeSMYKKLEevgrVEVYRHGgspw----strgVPKEVLIdaarrCEALVIFIGDvIDKEVLDAGEk-LKI 76  Pyrobaculum aeroph...
AEA12171    2 VCIFVSRDTFpeILYKKLAe--vGEVRAYPygkpa--wltagIPKDALKraaaeCDAMVVFVGDvVDREVLSSARn-LKI 76  Thermoproteus uzon...
ABP94433    2 YKVLVTRRIPg-PWLDLLKr--eTEVDIWEgr--------dpPPRSWILsrvkdKDGLLVTLTErVDREVIDAGVn-LKV 69  Metallosphaera sed...
ABX12308    3 KKVFLTRTLHd-FALKELKk--kYQIEVHKgk--------ipVPQSKLRskikdVDGLICFPYDiINKETIDLAEn-LKV 70  Nitrosopumilus mar...
Q9YAW4      4 PRVFVTREVFp-EALELLSk--yYDVEVWDky--------qpPPYETLLskareADALYTLLTDrIDCDLLSQAPr-LRI 71  Aeropyrum pernix K1
A1RYE4      4 PKVYVTRIIPe-PGLSMLKe--cCDVVVHEskd-------wpPSREELLrnirdKDALLCLLTDkIDAEVMDAAPn-LKV 72  Thermofilum penden...
ABK76950   37 KRILLTRRLQd-FAQARLGr--rYDLEVYSgr--------vpMPRRALIraisgAHALVCFPYDvIDAGVMDAAPd-LET 104 Cenarchaeum symbio...
ABW01681    1 MYLTRSTFPK--LLYDTLRna-gFDLEVWDnkghgmwdraaaPPRDVLRdaasrCDALVVTIGDrVDDYVLSNAK--VKV 75  Caldivirga maquili...
Feature 1          ##                          #                                              
1GDH_A     71 ISTYSIGFDHIDLDACKARGIKVGNAPhGVTVATAEIAMLLLLGSARRAGEgekmiRTRSWp----GWEPLELv---GEK 143 Hyphomicrobium met...
2GCG_A     80 ISTMSVGIDHLALDEIKKRGIRVGYTPdVLTDTTAELAVSLLLTTCRRLPEaieevKNGGWt----SWKPLWLc---GYG 152 human
NP_559036  77 VSTASVGVDHIDVEYAKRKGVVVAHTPyVLVDAVADLAVGLLIAVTRKIALgdrliRSGAAd----AVWGSLM----GVN 148 Pyrobaculum aeroph...
AEA12171   77 ISTVSVGYDHIDVAEARRRGIVVTNTPeVLVDATADLAVGLLLALVRRIVEg---dRLIRE-----GKAYDIWgaliGSD 148 Thermoproteus uzon...
ABP94433   70 ISTYSVGFDHIDVKYALSKGIRVTNTPdVLTDATADLIFGLLLAVARRIVEgdrliRDGKWn---lPWYPEFMl---GKE 143 Metallosphaera sed...
ABX12308   71 ISTYSVGFDHIDTKYAKGKKIRVGYTPeVLTDATADLAFSLLLDSLRRVSEgdriiRDGKW-----KMIYGAHdy-vGVD 144 Nitrosopumilus mar...
Q9YAW4     72 VAQMAVGFDNIDVECATRLGIYVTNTPgVLTEATAEFTWALILAAARRVVEadhfvRWGEWwrlrtGWHPMMMl---GVE 148 Aeropyrum pernix K1
A1RYE4     73 ISTYSVGFDHIDIPEATKRGIYVTHTPgVLTDAVAEFTVGLILAVTRRIVEadkiiRTGQWd---kPWNPYFLt---GPE 146 Thermofilum penden...
ABK76950  105 IATYSVGYDHIDVAHARGRGITVGYTPdVLTDATADLTMALMLDLLRRVTEgdriiRAGRWrq--iYGADDYL----GTD 178 Cenarchaeum symbio...
ABW01681   76 IATYSVGYDHIDLDAATRRGIPVGYTPeVLVEAVADLAIGLIITLARRVIEgdrlvRSGEAy----KVWGEFL----GTE 147 Caldivirga maquili...
Feature 1              #####                  ###  #                            ###   ##      
1GDH_A    144 LDNKTLGIYGFGSIGQALAKRAQGFDM-DIDYFDTHRASssdeasyqatfHDSLDSLLSVSQFFSLNAPSTPETRYFFNK 222 Hyphomicrobium met...
2GCG_A    153 LTQSTVGIIGLGRIGQAIARRLKPFGVqRFLYTGRQPRPeeaae--fqaeFVSTPELAAQSDFIVVACSLTPATEGLCNK 230 human
NP_559036 149 LRGKRAGIVGLGNIGVAIARRLKAFDI-EVAYWSRRRKPevefa--lgieYMELDSLLSSSDFIFLTMALTPETRWFFNR 225 Pyrobaculum aeroph...
AEA12171  149 IRGKRAGIVGLGNLGTAIARRLLAFGA-EVVYWSRTRKPqvefa--lgirYLPLDELLSTSDFVIVSVALTPETRHLMNW 225 Thermoproteus uzon...
ABP94433  144 VSHSTLGILGMGRIGRAVLRRAKGFDM-NVIYYSRKPHDvd-------akFVDLDTLLTESDFLVVTVDLNQETYHMLDY 215 Metallosphaera sed...
ABX12308  145 LQGKTIGILGLGRIGQTLAKRAKAFDM-DIIYHNRNRLSktker-tldakYVSFERLISQSDVISIHVPHTKETDKMFNM 222 Nitrosopumilus mar...
Q9YAW4    149 LRGKTLGILGMGRIGSRVAEIGKAFGM-RIIYHSRSRKReieke--lgaeYRSLEDLLRESDILSIHLPLTDETRHLIGE 225 Aeropyrum pernix K1
A1RYE4    147 LKGKTIGLVGLGRIGVATAKRLSSFDV-KILYYDIERRWdvetv-ipnmeFTDLDTLLEKSDIVSIHVPLTKETYHLINE 224 Thermofilum penden...
ABK76950  179 VGGKTLGILGMGRIGSRVAKRAAAFGM-KVIYHSRSSTGpg--------tRVTLGRLLERSDVLSIHVPHTPDTHEMMDM 249 Cenarchaeum symbio...
ABW01681  148 VWGKTLGILGLGNIGAAVARRAKAFNM-NVIYWSRTRKPwieva--lglrYVDLNELFRQSDYLVLTVALSKETYHIVNE 224 Caldivirga maquili...
Feature 1                   ###                       ##                      # ##            
1GDH_A    223 ATIKSLPQGAIVVNTARGDLVDNELVVAALEAGrLAYAGFDVFAGEPNi-NEGYYDLPNTFLFPHIGSAATQAREDMAHQ 301 Hyphomicrobium met...
2GCG_A    231 DFFQKMKETAVFINISRGDVVNQDDLYQALASGkIAAAGLDVTSPEPLptNHPLLTLKNCVILPHIGSATHRTRNTMSLL 310 human
NP_559036 226 ERFAKVKRGAYFINVARGGLVDTDALIEALEAGvLAGAALDVFDVEPLpaRHKLASMDNVVLTPHIGSATVETRRRMAEL 305 Pyrobaculum aeroph...
AEA12171  226 ERFSKMKRGAYFVNVARGPVVDTEALLRALREGiLAGAALDVYEVEPLphTHELVGMPNVVLTPHIGSAALETRIKMAEV 305 Thermoproteus uzon...
ABP94433  216 SKLMKMKRTAFLVNASRGPVVKEEDLVRVLSEGrIAGAALDVFEREPIspDNPLVKFPNVVLTPHLGSATRETREKMAEI 295 Metallosphaera sed...
ABX12308  223 KIFKKMKNTAFLINTSRGKVVNEKDLVTALKKKiIAGAGLDVFEQEPIskNHPLTKLQNVVLAPHIGSSTKETRAKMAEI 302 Nitrosopumilus mar...
Q9YAW4    226 SELKLMKKTAILVNTGRGAIVDTGALVKALREGwIAAAALDVFEEEPLnpNHPLTAFKNVVLAPHAASATRETRLRMAMM 305 Aeropyrum pernix K1
A1RYE4    225 ERLRKMKKTAYLINTARGPVVDTEALVKALKEGwIAGAALDVFEQEPLppNHPLTKFDNVVLAPHIASATIEARQRMAEL 304 Thermofilum penden...
ABK76950  250 SRLRKMKRSAYLINTSRGRVVHEKDLAAALRQGiIAGAALDVFHSEPVgpANPLVKMQNVVLAPHIGSSTDGTRRKMAEL 329 Cenarchaeum symbio...
ABW01681  225 ERLRLMKNTSYLVNVARGAVVDTNALVKALKEGwIAGAALDVYEEEPIpnTHELIKLNNVILTPHIASATVETRNKMAEV 304 Caldivirga maquili...
Feature 1                
1GDH_A    302 ANDLIDALFGG 312 Hyphomicrobium methylovorum
2GCG_A    311 AANNLLAGLRG 321 human
NP_559036 306 AAENVVSFFRT 316 Pyrobaculum aerophilum str. IM2
AEA12171  306 AAENVVRFFRG 316 Thermoproteus uzoniensis 768-20
ABP94433  296 AVKNLLNCLKG 306 Metallosphaera sedula DSM 5348
ABX12308  303 TVRNLNLGMNG 313 Nitrosopumilus maritimus SCM1
Q9YAW4    306 AAENLVAFAQG 316 Aeropyrum pernix K1
A1RYE4    305 AARNLIAVLKG 315 Thermofilum pendens Hrk 5
ABK76950  330 TVKNLELGLSG 340 Cenarchaeum symbiosum A
ABW01681  305 TALNVINVLLK 315 Caldivirga maquilingensis IC-167

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