1MC5,1TEH


Conserved Protein Domain Family
alcohol_DH_class_III

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cd08300: alcohol_DH_class_III 
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class III alcohol dehydrogenases
Members identified as glutathione-dependent formaldehyde dehydrogenase(FDH), a member of the zinc dependent/medium chain alcohol dehydrogenase family. FDH converts formaldehyde and NAD(P) to formate and NAD(P)H. The initial step in this process the spontaneous formation of a S-(hydroxymethyl)glutathione adduct from formaldehyde and glutathione, followed by FDH-mediated oxidation (and detoxification) of the adduct to S-formylglutathione. MDH family uses NAD(H) as a cofactor in the interconversion of alcohols and aldehydes or ketones. Like many zinc-dependent alcohol dehydrogenases (ADH) of the medium chain alcohol dehydrogenase/reductase family (MDR), these FDHs form dimers, with 4 zinc ions per dimer. The medium chain alcohol dehydrogenase family (MDR) have a NAD(P)(H)-binding domain in a Rossmann fold of a beta-alpha form. The N-terminal region typically has an all-beta catalytic domain. These proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and have 2 tightly bound zinc atoms per subunit. Alcohol dehydrogenase in the liver converts ethanol and NAD+ to acetaldehyde and NADH, while in yeast and some other microorganisms ADH catalyzes the conversion acetaldehyde to ethanol in alcoholic fermentation. ADH is a member of the medium chain alcohol dehydrogenase family (MDR), which have a NAD(P)(H)-binding domain in a Rossmann fold of a beta-alpha form. The NAD(H)-binding region is comprised of 2 structurally similar halves, each of which contacts a mononucleotide. A GxGxxG motif after the first mononucleotide contact half allows the close contact of the coenzyme with the ADH backbone. The N-terminal catalytic domain has a distant homology to GroES. These proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and have 2 tightly bound zinc atoms per subunit, a catalytic zinc at the active site and a structural zinc in a lobe of the catalytic domain. NAD(H) binding occurs in the cleft between the catalytic and coenzyme-binding domains at the active site, and coenzyme binding induces a conformational closing of this cleft. Coenzyme binding typically precedes and contributes to substrate binding.
Statistics
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PSSM-Id: 176260
View PSSM: cd08300
Aligned: 56 rows
Threshold Bit Score: 623.867
Threshold Setting Gi: 211962074
Created: 24-Dec-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 22 residues -Click on image for an interactive view with Cn3D
Feature 1:NAD binding site [chemical binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                ##                                      
1MC5_A         6 IKCKAAVAWEagKPLSIEEIEVAPPKAhEVRIKIIATAVCHTDAYTLSGADPEGCFPVILGHEGAGIVESVGEGVTkLKA 85  human
CAL57555       8 ITCKAAVAFApkQPLEVVDVVVAPPQAgEVRIKIMFTALCHTDAYTLDGFDSEGKFPCVLGHEAAGVVESVGSGVTsCKP 87  Ostreococcus tauri
XP_001771825  23 ITCRAAIAYEksKPLVIENVEVAPPQAgEVRVKILYTALCHTDFYTLSGKDPEGLFPCILGHEAAGVVESVGEGVTeLKP 102 Physcomitrella ...
Q96533         8 ITCKAAVAYEpnKPLVIEDVQVAPPQAgEVRIKILYTALCHTDAYTWSGKDPEGLFPCILGHEAAGIVESVGEGVTeVQA 87  thale cress
XP_001693934   8 IECKAAIAWEakKPLEVRTVTVAPPGPgEVRVQIKATALCQTDAYTLGGLDPEGRFPCILGHEAAGVVESVGEGVTsVKP 87  Chlamydomonas r...
EEA97269      14 ITCKAVVCFApgDPLQVTDIVVAPPKEgEVRIKILYAALCHTDEFARSGVDPEVTFPCILGHEAVGVVESVGKNVStCAV 93  Toxoplasma gond...
A2XAZ3        10 ITCKAAVAWEanKPMTIEDVQVAPPQAgEVRVKILFTALCHTDHYTWSGKDPEGLFPCILGHEAAGIVESVGEGVTeVQP 89  Indian rice
Q0DWH1        10 ITCKAAVAWEanRPMTIEDVQVAPPQAgEVRVKILFTALCHTDHYTWSGKDPEGLFPCILGHEAAGIVESVGEGVTeVQP 89  Japanese rice
P80572         7 ITCKAAVAWEpnKPLTIEDVEVAPPQAnEVRIQILFTALCHTDAYTLGGKDPEGLFPCILGHEAAGIVESVGEGVTdVKP 86  pea
P93629        10 ITCKAAVAYEpnKPLVIEDVQVAPPQAgEVRVKILFTALCHTDHYTWSGKDPEGLFPCILGHEAAGIVESVGEGVTdVQP 89  maize
Feature 1                                                                                        
1MC5_A        86 GDTVIPLYIP----------QCGECKFCLNPKTNLCQKir-vtQGKG-LMPDGTSRFTCk--GKTILHYMGTSTFSEYTV 151 human
CAL57555      88 GDRVIPCYQAyca-----diSENPCEHCLHPKSNLCQAvr-awTGRGvMKTDEKPRFTLardGSEIFHFMGTSTFSEYTV 161 Ostreococcus tauri
XP_001771825 103 GDHVIPCYQA----------ECRECKFCKSGKTNLCGKvr-paTGKGvMLSDGQSRFKVa--GKPIYHFMGTSTFSEYTV 169 Physcomitrella ...
Q96533        88 GDHVIPCYQA----------ECRECKFCKSGKTNLCGKvrsatGVGI-MMNDRKSRFSVn--GKPIYHFMGTSTFSQYTV 154 thale cress
XP_001693934  88 GDHVIPCYQA----------YCGECKFCKHPESNLCVSvr-afTGKGvMKSDGKPRFTVd--GKPIYHFMGTSTFSEYTV 154 Chlamydomonas r...
EEA97269      94 GDLVIPSFMPecfaedfkarTCAMCEGFEKHKTHLCGKir-rfTAQGvMAADGRPRFSLqtdGSPVYHFMGTSAFSEYTV 172 Toxoplasma gond...
A2XAZ3        90 GDHVIPCYQA----------ECRECKFCKSGKTNLCGKvr-aaTGVGvMMNDRKSRFSIn--GKPIYHFMGTSTFSQYTV 156 Indian rice
Q0DWH1        90 GDHVIPCYQA----------ECRECKFCKSGKTNLCGKvr-aaTGVGvMMNDRKSRFSIn--GKPIYHFMGTSTFSQYTV 156 Japanese rice
P80572        87 GDHVIPSYQA----------ECGECKFCKSPKTNLCGKvr-aaTGVGvMMADRKSRFSVk--GKPIYHFMGTSTFSQYTV 153 pea
P93629        90 GDHVIPCYQA----------ECKECKFCKSGKTNLCGKvr-saTGVGvMMNDMKSRFSVn--GKPIYHFMGTSTFSQYTV 156 maize
Feature 1                               #   #                    #####                   ##   #  
1MC5_A       152 VADISVAKIDPl-APLDKVCLLGCGISTGYGAAVNTAKLePGSVCAVFGLGGVGLAVIMGCKVAGAsRIIGVDINKDKFA 230 human
CAL57555     162 VHEVAVAKVNNdaAPLDKVCLLGCGVSTGWGAVHNTAGVeAGSTVAVFGLGAVGLACIEAAVEAGArQIIGVDTNDEKEA 241 Ostreococcus tauri
XP_001771825 170 LHDVSVAKINPd-APLDKVCLLGCGIPTGLGAVFNTAKVePGSNVAVFGLGTVGLAVCEGAKKAGAkRIIGVDTDPSKFD 248 Physcomitrella ...
Q96533       155 VHDVSVAKIDPt-APLDKVCLLGCGVPTGLGAVWNTAKVePGSNVAIFGLGTVGLAVAEGAKTAGAsRIIGIDIDSKKYE 233 thale cress
XP_001693934 155 VHEQSVAKIDVn-APLDKVCLLGCGVSTGWGAVFNTAKVtAGSTVAVFGLGAVGLAVIEAAKRAGAsRIIAVDINPTKFP 233 Chlamydomonas r...
EEA97269     173 SHQESVAVIPAn-APPEKVCLLGCGVATGLGAVWNTANVeAGSTVAVLGLGCVGLACVQAARRRGAkEILAVDKNKGKFE 251 Toxoplasma gond...
A2XAZ3       157 VHDVSVAKINPq-APLDKVCLLGCGVSTGLGAVWNTAKVeAGSIVAIFGLGTVGLAVAEGAKSAGAsRIIGIDIDSKKFD 235 Indian rice
Q0DWH1       157 VHDVSVAKINPq-APLDKVCLLGCGVSTGLGAVWNTAKVeAGSIVAIFGLGTVGLAVAEGAKSAGAsRIIGIDIDSKKFD 235 Japanese rice
P80572       154 VHDVSVAKIHPd-APLDKVCLLGCGVPTGLGAVWNTAKVePGSIVAIFGLGTVGLAVAEGAKSAGAsRIIGIDIDSNKYD 232 pea
P93629       157 VHDVSVAKINPq-APLDKVCLLGCGVPTGLGAVWNTAKVeSGSVVAVFGLGTVGLAVAEGAKAAGAsRVIGIDIDNKKFD 235 maize
Feature 1                                              ##   ##                 ##                
1MC5_A       231 RAKEFGATECINPQDFSk-pIQEVLIEMTDGGVDYSFECIGNVKVMRAALEACHKGWGVSVVVGVAasGEEIATRPFQLV 309 human
CAL57555     242 IARQFGATDFVNPTKFPgkdTQSVIVEMTNGGVDYSFECVGNVNVMRSALECCRKGWGTSVIVGVAaaGTEISTRPFQLV 321 Ostreococcus tauri
XP_001771825 249 LAVKFGATEYVNPKDFDk-pIQDVLVEMTDGGVDYSFECIGNVQVMRAALEACHKGWGTSVIVGVAaaGQEISTRPFQLV 327 Physcomitrella ...
Q96533       234 TAKKFGVNEFVNPKDHDk-pIQEVIVDLTDGGVDYSFECIGNVSVMRAALECCHKGWGTSVIVGVAasGQEISTRPFQLV 312 thale cress
XP_001693934 234 AAKEFGATDCINPKDHEk-pIQQVIVEMTEWGCDYTFECIGNTAVMRAALECAHRGWGTSVIVGVAaaGQEISTRPFQLV 312 Chlamydomonas r...
EEA97269     252 LARTMGATKCIDPAEYEdrpIQEVIAELTNGGVDYAFECVGNQHLMRACLECTHKGWGVGTIVGVC--AKEVSTRPFNLI 329 Toxoplasma gond...
A2XAZ3       236 VAKNFGVTEFVNPKDHDk-pIQQVIVDLTDGGVDYSFECIGNVSVMRSALECCHKGWGTSVIVGVAasGQEISTRPFQLV 314 Indian rice
Q0DWH1       236 VAKNFGVTEFVNPKDHDk-pIQQVIVDLTDGGVDYSFECIGNVSVMRSALECCHKGWGTSVIVGVAasGQEISTRPFQLV 314 Japanese rice
P80572       233 TAKNFGVTEFINPKDHEk-pIQQVIIDLTDGGVDYSFECLGNVSVMRSALECCHKGWGTSVIVGVAasGQEISTRPFQLV 311 pea
P93629       236 VAKNFGVTEFVNPKEHDk-pIQQVLVDLTDGGVDYSFECIGNVSIMRAALECSDKGWGTSVIVGVAasGQEISTRPFQLV 314 maize
Feature 1               ###                                                   #    
1MC5_A       310 TGRTWKGTAFGGWKSveSVPKLVSEYMSKKIKVDe--FVTHNLSFDEINKAFELMHSGKSIRTVVK 373 human
CAL57555     322 TGRTWKGTAFGGYKSrvAVPKLVEKVMSGGDKANldkYITHRMKFEQINEAFDLLHAGKCLRCVLS 387 Ostreococcus tauri
XP_001771825 328 TGRVWKGTAFGGYKSrtDVPKLVDEYMKQEIKLDe--YITHKFPLGKINEAFGLLEAGKCLRAVIN 391 Physcomitrella patens subsp. ...
Q96533       313 TGRVWKGTAFGGFKSrtQVPWLVEKYMNKEIKVDe--YITHNLTLGEINKAFDLLHEGTCLRCVLD 376 thale cress
XP_001693934 313 TGRRWMGTAFGGYKSrvQVPDLVTDYMSGATLLDk--YITHNMKFDQINEAFELLHAGECLRCVLT 376 Chlamydomonas reinhardtii
EEA97269     330 VGRTWKGSAFGGWRVrtHVPQLVQMYLDGEIKLDe--FISHRMELSEVNGAIRLLHAGDGIRTVLK 393 Toxoplasma gondii ME49
A2XAZ3       315 TGRVWKGTAFGGFKSrsQVPWLVEKYLNKEIKVDe--YVTHSMNLTDINKAFDLLHEGGCLRCVLA 378 Indian rice
Q0DWH1       315 TGRVWKGTAFGGFKSrsQVPWLVEKYLNKEIKVDe--YVTHSMNLTDINKAFDLLHEGGCLRCVLA 378 Japanese rice
P80572       312 TGRVWKGTAFGGFKSrsQVPWLVEKYLKKEIKVDe--YITHNLTLLEINKAFDLLHEGQCLRCVLA 375 pea
P93629       315 TGRVWKGTAFGGFKSrtQVPWLVDKYMKKEIKVDe--YITHNMNLADINDAFHLLHEGGCLRCVLA 378 maize

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