Conserved Protein Domain Family
Zn_ADH_class_III

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cd08279: Zn_ADH_class_III 
Class III alcohol dehydrogenase
Glutathione-dependent formaldehyde dehydrogenases (FDHs, Class III ADH) are members 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. NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes or ketones. 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. Class III ADH are also known as glutathione-dependent formaldehyde dehydrogenase (FDH), which convert aldehydes to corresponding carboxylic acid and alcohol. ADH is a member of the medium chain alcohol dehydrogenase family (MDR), which has a NAD(P)(H)-binding domain in a Rossmann fold of an 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: 176240
View PSSM: cd08279
Aligned: 54 rows
Threshold Bit Score: 418.483
Threshold Setting Gi: 111224833
Created: 4-May-2009
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
Feature 1:NAD binding site [chemical binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                               ###  #                                   
YP_002521996   3 ARAAVLAEvk--kPLEIWELEVDAPKEGEVLVRVVAAGVCHSDLHYIQGdle--tplPAIPGHEGAGVVEAVGPGVTrFR 78  Thermomicrobium...
NP_116811     12 SKAAIATGd---gAFIIDTTEVSSPQPDEVLVRIRAAGLCHTDHDSLRWg------kSIVMGHEGAGVVEQVGNQVDaLA 82  Microscilla sp....
YP_661878      8 SKAIVSNGr---gQYELVTLRVSAPGKGEVRVKIQASGLCHTDWDSIQNwd-----kTFVVGHEGAGVIDAVGEDVTgLN 79  Pseudoalteromon...
YP_885532     14 IRAAVFDG-----TISVEPVDLADPRPGEVRVKIAAAGVCHSDLHVTTGawd--vpaPVVLGHEGSGVVTAVGEGVDdLE 86  Mycobacterium s...
YP_001262586   1 MRAALLHQds--nTPRLEEVAVEEPRFGEVLVRIAASGICGSDLHVVHNrsnvgkdrPVILGHEGAGVVEAVGPGVRdLK 78  Sphingomonas wi...
YP_002777304   3 VKAAVFERvg--ePIHVEELDLEDPKRGEVLVRLEAAGVCHSDYHVVKGewe--sagPLVLGHEGAGVVEKIGPGVTsVS 78  Rhodococcus opa...
YP_003119406   1 MRAAVFEGg---kLEVVDGIEVRAPRTDEIVVRVGAAGLCHSDLSVVNGtip--fpgPAVLGHEGAGVVEEVGGAVTrVK 75  Catenulispora a...
NP_827048      1 MRAAVLHEigqdkLEVLDDVESVGFGPGRVRIRVRATGLCHSDLSAMSGvlp--qpaPFVPGHEGAGEIVEVGEGVShLK 78  Streptomyces av...
YP_001159422   1 MRAAIFHTvgddkVEIRDDVTVIGPGAGEVRIRVRAAGVCHSDRSTRDGvlp--hpmPVVLGHEASGDVVAVGDGVEdLA 78  Salinispora tro...
YP_002777067   1 MRAVVIWNpg-epFTIHDNVCRPAPGPGEVVVRIRAAGVCQTDIALSKGafg--qstPVVLGHEGAGEITELGPGVTgLI 77  Rhodococcus opa...
Feature 1                                                                                        
YP_002521996  79 PGDPVVFVFRAfCGHCFYClNGRPALCDfsnpir----rtgrmfDGTTRFHRNGTDVHHVLGVSCFAEYTVVPEQGLLSL 154 Thermomicrobium...
NP_116811     83 PGDKVILNWATpCMQCYQCqEGNQHICEnhspvaaganghtpghAHLEGTQWQGKPIERSFNIGTLSEYTLVKASACVKM 162 Microscilla sp....
YP_661878     80 VGDKVILNWSIpCGHCFACqQGNVHICEnnspvcg---nglcghAHASATTQSGTAIERSFHLGTLSEYTVVKAAAIVKF 156 Pseudoalteromon...
YP_885532     87 PGDHVVLSWVPgCGECRYCkAGRPAQCSlvasvva---vkgtlyDGTTRLSNERGTVHHYLGVSSYAEQVVVPRNGAIKV 163 Mycobacterium s...
YP_001262586  79 RGDHVVMAMFGpCGHCDPCnSGKLQFCDgpefks----avgrmaDDSTRFSQDGRMVFPMVGVGSLAEYAVMREAMLVKV 154 Sphingomonas wi...
YP_002777304  79 VGDHVVLSWVPyCGTCAYCmAGKPALCPkveeta----yqnvqyDGTSRLSRGDESVPSYLATGAFADRVIVHETGAVPI 154 Rhodococcus opa...
YP_003119406  76 PGDHVCLTTINhCGVCPACsEGRPTMCRatfgk-------iskpFTREAADGTAEKLFAFANTSVFTERVVVKEVQAVPI 148 Catenulispora a...
NP_827048     79 PGDRVVVCWLPaCGVCPACkRGQSQLCLagf-----------mnAGTPNFRRPGGDVFGFAGTGTFAEEVVVDAGSAVPI 147 Streptomyces av...
YP_001159422  79 EGDRVVVNWLPaCGSCPSCaRGESYLCLanv----------lagYAQPRFLAGQTPVFAMAGCGAFAEEIVIPRAGAVKV 148 Salinispora tro...
YP_002777067  78 PGDRVLVTWVPpCGRCYHCvRGETYICSnrrr--------sserGDEGSLSVSGVPVQAGMGTATFAEETVVPATGVLPL 149 Rhodococcus opa...
Feature 1                     #   #                    #####                   ##   #            
YP_002521996 155 PPdiPLDRAALVGCGVTTGVGAVLFAAGVrAGETVLVIGCGGVGLNVVQGAALVGAGPVIAADVVPQKLEWARQLGATHT 234 Thermomicrobium...
NP_116811    163 DGdiPMSSASIISCGVMTGYGSVVNSARLtAGSSSVVLGTGGVGLNVIQGCRISGASKIIAIDINPQRLEMAKVFGATHT 242 Microscilla sp....
YP_661878    157 EHdiPFSSASIVGCGVMTGYGSVVNAAQVkAGSTVCVIGCGGVGLNVIQAARISGARKIIAIDINQERLEQAKAFGATHG 236 Pseudoalteromon...
YP_885532    164 RKdaPLEDIAIVGCAIATGVGAVRNTAGVePGSTVAVIGCGGVGLACVQGARLAGASRIVAVDVVAEKLELARKLGATDA 243 Mycobacterium s...
YP_001262586 155 APhlPLDRLCFCACSVTTGLGAVFNVAKVtPGTSVAVIGCGGVGLNVIQGARIAGASRIIAIDTNRAKLDIASNMGATDL 234 Sphingomonas wi...
YP_002777304 155 RKdaPLDRAALVGCAVATGVGAVLNTADVqPGDTVLVFGCGGVGLSVIMGAGLVSAGQIIAVDMSDKALELAKSLGATAI 234 Rhodococcus opa...
YP_003119406 149 PEdvPMASAALVGCGVLTGVGAVLNRAKVrIGETVVVIGVGGIGLNAIQGARIARAGRIVAIDTNPRKEEAARRFGATDF 228 Catenulispora a...
NP_827048    148 PDdvPFDIAALIGCGVTTGLGAALNTADVaAGSSVAVIGCGGVGISAVQGARLKGAAEIVAVDPVASRRESALRFGATQA 227 Streptomyces av...
YP_001159422 149 APdvPYEVAALVGCGVMTGVGAVINTARVePGAAVAVIGCGGVGIAAIQGARLAGAAVIVAVDTVEAKQQTALRFGATHG 228 Salinispora tro...
YP_002777067 150 PDdiPFEYAALLGCAVPTGCGAALNSARVrAGESVLVIGCGAVGLSAIQGAVIAGAADIVAVDPQDPRRRAALEFGATAA 229 Rhodococcus opa...
Feature 1                                       ###   #                ###                       
YP_002521996 235 IDPreq-----dvVEVVRELTgGRGADYAFEVIGRaDTIQQAYAATRKGGTTVIVGLtpm--gttVPLDPLDLlrtEKTI 307 Thermomicrobium...
NP_116811    243 ILAdkndlglmqaSEEVKKLTsGRGADYAFECTAIsALGAAPLAMIRNAGTAVQVSGie----eeITIDMRLFe-wDKLY 317 Microscilla sp....
YP_661878    237 IISiqndldfaqmSALVKELTqGRGADYAFECTAIpALGSAPLALIRNAGTAVQVSGie----qrIDFNCELFe-wDKIY 311 Pseudoalteromon...
YP_885532    244 VDAsat----ddvVAAMREVL-PDGYDYVFDAIGKiATTEQAIAALGLGGAAVIVGLppq--gerASFDPLTLaeaDQRI 316 Mycobacterium s...
YP_001262586 235 IQSggdp---aevDAAVKALQ-PRGVDFAFEVVGNhALIRQAVGFTGRGGTTVMIGGvpw--asdVSVNAGLLf-gERKL 307 Sphingomonas wi...
YP_002777304 235 INPsrd-----dvATTVRGLVdERGVDWAFEAIGLkPTIEQAYELISPGGTVVVVGQsad--gvtIEIDPMVMsdrEKSI 307 Rhodococcus opa...
YP_003119406 229 LDPsgq-----daVELVKELL-PRGADYVFECVGHpALIRAATDMLAWSGAAVLLGVprsdaegtFLVSGMYM---DKTI 299 Catenulispora a...
NP_827048    228 VSPde-------lAAAKQAVTgGEGFDYVFEVVGRsATARTAYENTRRGGTLVVVGAgal--ddfLQLNMFELffdEKRI 298 Streptomyces av...
YP_001159422 229 CGPet-------lSELSAQLTdGEGFDTVFDVVAVpQTLRAAWTAARRGGAVVVVGAgrs--dqqVAFSPFELlfeGKTI 299 Salinispora tro...
YP_002777067 230 LPPg---------SDPRESLVdAPGFDVVIDAVARsSTIRDGWQAARRGGRVVVVGAgkp--ddmVQFSAQELfhdGKQL 298 Rhodococcus opa...
Feature 1          ###                                          #      #    
YP_002521996 308 KATLYGSANLprDIPRLLELYRLGRLRLDeLISRRLRLEEINDGFEAMLAGsvARSIVV 366 Thermomicrobium roseum DSM 5159
NP_116811    318 INPLYGKCRPqlDFPKLESLYHKGELKLDeMITRTYQLEDLQQAFDDMLSGknAKGVIV 376 Microscilla sp. PRE1
YP_661878    312 MNPLYGKCNPqtDFPALLDLYSNGQLKLDeLVTKTYSLENVADGFDDMLNGriAKGVII 370 Pseudoalteromonas atlantica T6c
YP_885532    317 LGSNYGSAVPerDIPALVDEVMAGNLDLAsMISGRRPLEEAAAALDDLAAGhaLRQLLI 375 Mycobacterium smegmatis str. MC2 155
YP_001262586 308 MGCLGGGNIPgrEIPRIVGLYERGMLKLDeLVGKTFDFDDIGEAIAEADRAqtAKTVVA 366 Sphingomonas wittichii RW1
YP_002777304 308 IGCNYGSSRPaiDFPRLIDLYMQGKLDLDrLVGHTSSINEVNEAFTRMGQGegGRTVIL 366 Rhodococcus opacus B4
YP_003119406 300 MGCRYGTSHPqfDVERYVDLYRKGELLLDeLVTKTYPLEHIHEAIHDLESGslARGVLL 358 Catenulispora acidiphila DSM 44928
NP_827048    299 LPSMYGGGDVlrSYERTIALWRAGRIDLEgLITHRVPLAEINEALDQMRTGtaLRTCIE 357 Streptomyces avermitilis MA-4680
YP_001159422 300 TSSLYGASQAprDFDRMFGLWRAGRLDLSeMITHRLRLEDVGDAFAALGRGdvIRQVIC 358 Salinispora tropica CNB-440
YP_002777067 299 IGSFYGSSDMrrELPRLIALWRAGRLDLSrMVSEVVDLERINDVVARQTAGevVRSVLL 357 Rhodococcus opacus B4

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