1BXS,2H5G,2BJA,1UXU,1T90,1AD3,3B4W,2J6L,2IMP,1EYY,2JG7,1CW3,2VRO,2ESD,1BPW,2O2Q,1WNB,2D4E,3EK1,3FG0


Conserved Protein Domain Family
ALDH-SF

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cd06534: ALDH-SF 
Click on image for an interactive view with Cn3D
NAD(P)+-dependent aldehyde dehydrogenase superfamily
The aldehyde dehydrogenase superfamily (ALDH-SF) of NAD(P)+-dependent enzymes, in general, oxidize a wide range of endogenous and exogenous aliphatic and aromatic aldehydes to their corresponding carboxylic acids and play an important role in detoxification. Besides aldehyde detoxification, many ALDH isozymes possess multiple additional catalytic and non-catalytic functions such as participating in metabolic pathways, or as binding proteins, or osmoregulants, to mention a few. The enzyme has three domains, a NAD(P)+ cofactor-binding domain, a catalytic domain, and a bridging domain; and the active enzyme is generally either homodimeric or homotetrameric. The catalytic mechanism is proposed to involve cofactor binding, resulting in a conformational change and activation of an invariant catalytic cysteine nucleophile. The cysteine and aldehyde substrate form an oxyanion thiohemiacetal intermediate resulting in hydride transfer to the cofactor and formation of a thioacylenzyme intermediate. Hydrolysis of the thioacylenzyme and release of the carboxylic acid product occurs, and in most cases, the reduced cofactor dissociates from the enzyme. The evolutionary phylogenetic tree of ALDHs appears to have an initial bifurcation between what has been characterized as the classical aldehyde dehydrogenases, the ALDH family (ALDH) and extended family members or aldehyde dehydrogenase-like (ALDH-L) proteins. The ALDH proteins are represented by enzymes which share a number of highly conserved residues necessary for catalysis and cofactor binding and they include such proteins as retinal dehydrogenase, 10-formyltetrahydrofolate dehydrogenase, non-phosphorylating glyceraldehyde 3-phosphate dehydrogenase, delta(1)-pyrroline-5-carboxylate dehydrogenases, alpha-ketoglutaric semialdehyde dehydrogenase, alpha-aminoadipic semialdehyde dehydrogenase, coniferyl aldehyde dehydrogenase and succinate-semialdehyde dehydrogenase. Included in this larger group are all human, Arabidopsis, Tortula, fungal, protozoan, and Drosophila ALDHs identified in families ALDH1 through ALDH22 with the exception of families ALDH18, ALDH19, and ALDH20 which are present in the ALDH-like group. The ALDH-like group is represented by such proteins as gamma-glutamyl phosphate reductase, LuxC-like acyl-CoA reductase, and coenzyme A acylating aldehyde dehydrogenase. All of these proteins have a conserved cysteine that aligns with the catalytic cysteine of the ALDH group.
Statistics
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PSSM-Id: 143395
View PSSM: cd06534
Aligned: 67 rows
Threshold Bit Score: 169.717
Threshold Setting Gi: 126517
Created: 8-Jan-2008
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 4 residues -Click on image for an interactive view with Cn3D
Feature 1:catalytic residues [active site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                                     
1BXS_A     65 KAARQAFQigspwrtmDASERGRLLNKLADLIErDRLLLATMEAMnggkl----------fsnaYLMDLGGCIKTLRyca 134 sheep
2H5G_A     36 EXARSGGRxla---tlEPEQRAEIIHHLADLLTdQRDEILLANKKdleeaegrlaapllkrlslSTSKLNSLAIGLRqia 112 human
1UXU_A     61 DVLFKRGRwsa--rdmPGTERLAVLRKAADIIErNLDVFAEVLVMnagk-----------pksaAVGEVKAAVDRLRlae 127 Thermoproteus tenax
1EYY_A     37 TAAAKVARdfr---rlNNSKRASLLRTIASELEaRSDDIIARAHLetal-----------pevrLTGEIARTANQLRlfa 102 Vibrio harveyi
2VRO_B     48 SFAREDGGaal--ralTYAQRAARLADIVKLLQaKRGDYYAIATAnsgt-----------trndSAVDIDGGIFTLSyya 114 Burkholderia xenov...
Q8IZ83     84 EAARMAFKgws---ahPGVVRAQHLTRLAEVIQkHQRLLWTLESLvtgra----------vrevRDGDVQLAQQLLHyha 150 human
Q7ADE6     44 RAARAAFPrwa---rlSFAERQAVVERFAGLLErNKGELTAIIARetgk-----------prweAATELTAMINKIAisi 109 Escherichia coli O...
CAJ73105   48 LAAKTAYDtwr---kiSRIRRGEYLDELAQLLKkDREAISQLVSKecgk-----------giaeGRADVTEGIHMVQyif 113 Candidatus Kueneni...
Q8VZC3    117 LYGDISTKaah---mlALPKVADFFARLIQRVApKSYQQAAGEVFvt---------------rkFLENFCGDQVRFLars 178 thale cress
AAG28964  102 DAAHAAMPgwq---riGAQGRAGVCLEILERLNkRSFEIAHAVMLttgq------------gwmMAFQAGGPHAQDRgle 166 Azoarcus evansii
Feature 1                                                      #                              
1BXS_A    135 gwadkiqg-------------rtipmdgnffTYTRse-pvGVCGQIIPWNFPllm--flWKIGPALSCGNTVVVKPAEqt 198 sheep
2H5G_A    113 assqdsvgr----------vlrrtriaknleLEQVtv-piGVLLVIFESRPDcl----pQVAALAIASGNGLLLKGGKea 177 human
1UXU_A    128 ldlkkiggdy--------ipgdwtydtleteGLVRre-plGVVAAITPFNYPlfd--avNKITYSFIYGNAVVVKPSIsd 196 Thermoproteus tenax
1EYY_A    103 dvvnsgsyhqai----ldtpnptraplpkpdIRRQqi-alGPVAVFGASNFPlafsaagGDTASALAAGCPVIVKGHTah 177 Vibrio harveyi
2VRO_B    115 klgaslgevhal----rdgsaeslskdrsfsAQHVlsptrGVALFINAFNFPswg--lwEKAAPALLSGVPVIVKPATat 188 Burkholderia xenov...
Q8IZ83    151 iqa-----------------------stqeeALAGwe-pmGVIGLILPPTFSfle--mmWRICPALAVGCTVVALVPPas 204 human
Q7ADE6    110 kayhvrtg-------------eqrsempdgaASLRhr-phGVLAVFGPYNFPghl--pnGHIVPALLAGNTIIFKPSElt 173 Escherichia coli O...
CAJ73105  114 gttrmphg------------diidseivekdSFMRrr-pkGVVAAITPWNFPfai--plWLICPSVVEGNTVVLKPSRet 178 Candidatus Kueneni...
Q8VZC3    179 faip--------------------gnhlgqqSHGYrw-pyGPVTIVTPFNFPlei--plLQLMGALYMGNKPLLKVDSkv 235 thale cress
AAG28964  167 avayayremkfiphetvwekpqgknpplkmkKHFEiv-grGVALVIGCGTFPtwn--tyPGLFAALATGNPVIVKPHQna 243 Azoarcus evansii
Feature 1                                                                                 #   
1BXS_A    199 pltalHMGSLIKeagf----ppgVVNIVPgygptagaAISSHmd-vdKVAFTGSTEVGKLIKEAagks-nlkrVSLELGG 272 sheep
2H5G_A    178 ahsnrILHLLTQealsi-hgvkeAVQLVNtre--eveDLCRLdkxidLIIPRGSSQLVRDIQKAakg----ipVXGHSEG 250 human
1UXU_A    197 plpaaMAVKALLdagf----ppdAIALLNlpgk-eaeKIVADdr-vaAVSFTGSTEVGERVVKVggv----kqYVMELGG 266 Thermoproteus tenax
1EYY_A    178 pgtsqIVAECIEqalkqeqlpqaIFTLLQgnqralgqALVSHpe-ikAVGFTGSVGGGRALFNLaherpepipFYGELGA 256 Vibrio harveyi
2VRO_B    189 awltqRMVADVVdagi---lppgALSIICgs----saGLLDQirsfdVVSFTGSADTAATLRAHpafvqrgarLNVEADS 261 Burkholderia xenov...
Q8IZ83    205 p-aplLLAQLAGelgp----fpgILNVVSgpas-lvpILASQpg-irKVAFCGAPEEGRALRRSlage--caeLGLALGT 275 human
Q7ADE6    174 pwsgeAVMRLWQqagl----ppgVLNLVQggce-tgqALSALed-ldGLLFTGSANTGYQLHRQlsgq-pekiLALEMGG 246 Escherichia coli O...
CAJ73105  179 pcvanKIAEYVHaagf----ppgVINVIHggc--gdaLVRHSdt--qVILFTGSCEVGEGIKKIaaes-ynkmCACEMGG 249 Candidatus Kueneni...
Q8VZC3    236 sivmeQMMRLLHycgl----paeDVDFINsdgk-tmnKILLEan-prMTLFTGSSRVAEKLALDlk-----grIRLEDAG 304 thale cress
AAG28964  244 ilpaaITVRIARevlaeagldpnLVTLAAfdkheatqALATHpa-vkSIDFTGGNAFGQWLISNakq----aqVYAELAG 318 Azoarcus evansii
Feature 1                                     #  #                                            
1BXS_A    273 KSPCIVFAd-----aDLDNAVEFAHQGVFYhqGQCCIAASRLFVEes-----iYDEFVRRSVerakkyvlgnpltpgvsq 342 sheep
2H5G_A    251 ICHXYVDSe-----aSVDKVTRLVRDSKCEy-PAACNALETLLIHrdllrtplFDQIIDXLRv----------------- 307 human
1UXU_A    267 GDPAIVLEd-----aDLDLAADKIARGIYSyaGQRCDAIKLVLAErp-----vYGKLVEEVAkrlsslrvgdprdptvdv 336 Thermoproteus tenax
1EYY_A    257 INPTFIFPsa---mrAKADLADQFVASMTMgcGQFCTKPGVVFALnt----peTQAFIETAQslirqqspstlltpgird 329 Vibrio harveyi
2VRO_B    262 LNSAILCAdatpdtpAFDLFIKEVVREMTVksGQKCTAIRRAFVPea-----aLEPVLEALKaklakitvgnprndavrm 336 Burkholderia xenov...
Q8IZ83    276 ESLLLLTDt-----aDVDSAVEGVVDAAWSd-RGPGGLRLLIQESv-------WDEAMRRLQermgrlrsgrgldgavdm 342 human
Q7ADE6    247 NNPLIIDEv-----aDIDAAVHLTIQSAFVtaGQRCTCARRVLLKsg----aqGDAFLARLVavsqrltpgnwddepqpf 317 Escherichia coli O...
CAJ73105  250 KNAIIVLDg-----aNMEIAVNASILSAFKtsGQRCTSAGRLILHvn-----mLEEFEKRFVelakrikignpldeevfm 319 Candidatus Kueneni...
Q8VZC3    305 FDWKVLGPdv----qEVDYVAWQCDQDAYAcsGQKCSAQSMLFVHen----wsKTPLVSKLKelaerrkledltigpvlt 376 thale cress
AAG28964  319 VNNVVIESt-----dQYKAMLRNLAFTLCLysGQMCTTTQAILVPadgidtdqGRKSYDEVCadlatsidkfladpavat 393 Azoarcus evansii
Feature 1                                                                                     
1BXS_A    343 gpqidkeqyeki-----ldliesgkkegaklecgggpwgnkgyfiqpTVFSdvtddm-----------riakeEIFGPVQ 406 sheep
2H5G_A    308 ----------------------------------------------eQVKIhagpkfasyltfspsevkslrtEYGDLEL 341 human
1UXU_A    337 gplispsavde-------mmaaiedavekggrvlaggrrlgptyvqpTFVEapadrvk--------dmvlykrEVFAPVA 401 Thermoproteus tenax
1EYY_A    330 syqsqv------------------vsrgsddgidvtfsqaespcvasALFVtssenwr--------khpaweeEIFGPQS 383 Vibrio harveyi
2VRO_B    337 gslvsreqyenvlagiaalreeavlaydssavplidadaniaacvapHLFVvndpdna---------tllhdvEVFGPVA 407 Burkholderia xenov...
Q8IZ83    343 gargaaacdlv-------qrfvreaqsqgaqvfqagdvpserpfyppTLVSnlppas-----------pcaqvEVPWPVV 404 human
Q7ADE6    318 iggliseqaaqqv----ftawqqleamggrtllaprllqagtslltpGIIEmtgva------------gvpdeEVFGPLL 381 Escherichia coli O...
CAJ73105  320 gpvinqaatekilr-yndfaknegaevlldgsrltgggydkgyfmspFVYRmknnpk----------srvlheEVFGPHV 388 Candidatus Kueneni...
Q8VZC3    377 ftteamlehmenl----lqipgskllfggkelknhsipsiygaleptAVYVpieeilkdn-----ktyelvtkEIFGPFQ 447 thale cress
AAG28964  394 avlgaiqspdtla----riaeapahgrvvrastkiehaefpgaevrsPLLLacdaad----------ekaymeERFGPIA 459 Azoarcus evansii
Feature 1                                                                                     
1BXS_A    407 QIMKfk--------slDDVIKRANNTfygLSAGIFTnd--iDKAITVSSal--qsGTVWVNcysvv---------saqcp 465 sheep
2H5G_A    342 CIEVvd--------nvQDAIDHIHKYgssHTDVIVTed--eNTAEFFLQhv--dsACVFWNastrfsdgy-rfglgaevg 408 human
1UXU_A    402 LAVEvk--------dlDQAIELANGRpygLDAAVFGrd--vVKIRRAVRll--evGAIYINdmprhg--------igyyp 461 Thermoproteus tenax
1EYY_A    384 LIVVce--------nvADMLSLSEMLagsLTATIHAteedyPQVSQLIPrleeiaGRLVFNgwptgve------vgyamv 449 Vibrio harveyi
2VRO_B    408 SVAPyrvttdtnalpeAHAVALARRGqgsLVASIYSnd--dAHLGRLALeladshGRVHAIspsvqhsqtghgnvmpmsl 485 Burkholderia xenov...
Q8IZ83    405 VASPfr--------taKEALLVANGTprgGSASVWSer--lGQALELGYgl--qvGTVWINahglr---------dpsvp 463 human
Q7ADE6    382 RVWRyd--------sfEEAIRMANNTrfgLSCGLVSpe--rEKFDQLLLea--raGIVNWNkpltga--------astap 441 Escherichia coli O...
CAJ73105  389 AIIPve--------siDEAINVYNDTeygLSCAVITed--fRKARRIRDdc--eyGLGYVNlptiga--------evhlp 448 Candidatus Kueneni...
Q8VZC3    448 IVTEykk------dqlPLVLEALERMhahLTAAVVSnd--pIFLQEVIGns--vnGTTYAGlrgrtt--------gapqn 509 thale cress
AAG28964  460 FVVKvadg-----aaaVTLSERIVREhgaLTVGLYTtk--pEVVDAMTEatw-raGVALSInltggvfvn--qsagfsdy 529 Azoarcus evansii
Feature 1                                     
1BXS_A    466 FGGfkmsgngre---lgeygfheYTEVKTVTI 494 sheep
2H5G_A    409 ISTsriharg-------pvglegLLTTKWLLR 433 human
1UXU_A    462 FGGrkksgvfre---gigyaveaVTAYKTIVF 490 Thermoproteus tenax
1EYY_A    450 HGGpypasthsastsvgaeaihrWLRPVAYQA 481 Vibrio harveyi
2VRO_B    486 HGGpgragggee--lgglralafYHRRSAIQA 515 Burkholderia xenovorans
Q8IZ83    464 TGGckesgcswh---ggpdglyeYLRPSGTPA 492 human
Q7ADE6    442 FGGigasgnhr----psawyaadYCAWPMASL 469 Escherichia coli O157:H7 str. EC508
CAJ73105  449 FGGlkksgtglp---sastlidaVTHRTAWTV 477 Candidatus Kuenenia stuttgartiensis
Q8VZC3    510 HWFgpagdprgag-igtpeaiklVWSCHREVI 540 thale cress
AAG28964  530 HGVgmnpaana----slsdsafvANRFRVVQR 557 Azoarcus evansii

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