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

?
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
?
PSSM-Id: 143395
View PSSM: cd06534
Aligned: 67 rows
Threshold Bit Score: 169.717
Threshold Setting Gi: 126517
Created: 8-Jan-2008
Updated: 17-Jan-2013
Structure
?
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
?
Format: Row Display: Color Bits: Type Selection:
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                       
1BXS_A       65 KAARQAFQigspwrtmDASERGRLLNKLADLIErDRLLLATMEAMnggkl----------fsnaYLMDLGGCIKTLRyca 134
2H5G_A       36 EXARSGGRxla---tlEPEQRAEIIHHLADLLTdQRDEILLANKKdleeaegrlaapllkrlslSTSKLNSLAIGLRqia 112
1UXU_A       61 DVLFKRGRwsa--rdmPGTERLAVLRKAADIIErNLDVFAEVLVMnagk-----------pksaAVGEVKAAVDRLRlae 127
1EYY_A       37 TAAAKVARdfr---rlNNSKRASLLRTIASELEaRSDDIIARAHLetal-----------pevrLTGEIARTANQLRlfa 102
2VRO_B       48 SFAREDGGaal--ralTYAQRAARLADIVKLLQaKRGDYYAIATAnsgt-----------trndSAVDIDGGIFTLSyya 114
gi 74728442  84 EAARMAFKgws---ahPGVVRAQHLTRLAEVIQkHQRLLWTLESLvtgra----------vrevRDGDVQLAQQLLHyha 150
gi 75521601  44 RAARAAFPrwa---rlSFAERQAVVERFAGLLErNKGELTAIIARetgk-----------prweAATELTAMINKIAisi 109
gi 91200062  48 LAAKTAYDtwr---kiSRIRRGEYLDELAQLLKkDREAISQLVSKecgk-----------giaeGRADVTEGIHMVQyif 113
gi 75248520 117 LYGDISTKaah---mlALPKVADFFARLIQRVApKSYQQAAGEVFvt---------------rkFLENFCGDQVRFLars 178
gi 11072185 102 DAAHAAMPgwq---riGAQGRAGVCLEILERLNkRSFEIAHAVMLttgq------------gwmMAFQAGGPHAQDRgle 166
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                        #                              
1BXS_A      135 gwadkiqg-------------rtipmdgnffTYTRse-pvGVCGQIIPWNFPllm--flWKIGPALSCGNTVVVKPAEqt 198
2H5G_A      113 assqdsvgr----------vlrrtriaknleLEQVtv-piGVLLVIFESRPDcl----pQVAALAIASGNGLLLKGGKea 177
1UXU_A      128 ldlkkiggdy--------ipgdwtydtleteGLVRre-plGVVAAITPFNYPlfd--avNKITYSFIYGNAVVVKPSIsd 196
1EYY_A      103 dvvnsgsyhqai----ldtpnptraplpkpdIRRQqi-alGPVAVFGASNFPlafsaagGDTASALAAGCPVIVKGHTah 177
2VRO_B      115 klgaslgevhal----rdgsaeslskdrsfsAQHVlsptrGVALFINAFNFPswg--lwEKAAPALLSGVPVIVKPATat 188
gi 74728442 151 iqa-----------------------stqeeALAGwe-pmGVIGLILPPTFSfle--mmWRICPALAVGCTVVALVPPas 204
gi 75521601 110 kayhvrtg-------------eqrsempdgaASLRhr-phGVLAVFGPYNFPghl--pnGHIVPALLAGNTIIFKPSElt 173
gi 91200062 114 gttrmphg------------diidseivekdSFMRrr-pkGVVAAITPWNFPfai--plWLICPSVVEGNTVVLKPSRet 178
gi 75248520 179 faip--------------------gnhlgqqSHGYrw-pyGPVTIVTPFNFPlei--plLQLMGALYMGNKPLLKVDSkv 235
gi 11072185 167 avayayremkfiphetvwekpqgknpplkmkKHFEiv-grGVALVIGCGTFPtwn--tyPGLFAALATGNPVIVKPHQna 243
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                   #   
1BXS_A      199 pltalHMGSLIKeagf----ppgVVNIVPgygptagaAISSHmd-vdKVAFTGSTEVGKLIKEAagks-nlkrVSLELGG 272
2H5G_A      178 ahsnrILHLLTQealsi-hgvkeAVQLVNtre--eveDLCRLdkxidLIIPRGSSQLVRDIQKAakg----ipVXGHSEG 250
1UXU_A      197 plpaaMAVKALLdagf----ppdAIALLNlpgk-eaeKIVADdr-vaAVSFTGSTEVGERVVKVggv----kqYVMELGG 266
1EYY_A      178 pgtsqIVAECIEqalkqeqlpqaIFTLLQgnqralgqALVSHpe-ikAVGFTGSVGGGRALFNLaherpepipFYGELGA 256
2VRO_B      189 awltqRMVADVVdagi---lppgALSIICgs----saGLLDQirsfdVVSFTGSADTAATLRAHpafvqrgarLNVEADS 261
gi 74728442 205 p-aplLLAQLAGelgp----fpgILNVVSgpas-lvpILASQpg-irKVAFCGAPEEGRALRRSlage--caeLGLALGT 275
gi 75521601 174 pwsgeAVMRLWQqagl----ppgVLNLVQggce-tgqALSALed-ldGLLFTGSANTGYQLHRQlsgq-pekiLALEMGG 246
gi 91200062 179 pcvanKIAEYVHaagf----ppgVINVIHggc--gdaLVRHSdt--qVILFTGSCEVGEGIKKIaaes-ynkmCACEMGG 249
gi 75248520 236 sivmeQMMRLLHycgl----paeDVDFINsdgk-tmnKILLEan-prMTLFTGSSRVAEKLALDlk-----grIRLEDAG 304
gi 11072185 244 ilpaaITVRIARevlaeagldpnLVTLAAfdkheatqALATHpa-vkSIDFTGGNAFGQWLISNakq----aqVYAELAG 318
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                       #  #                                            
1BXS_A      273 KSPCIVFAd-----aDLDNAVEFAHQGVFYhqGQCCIAASRLFVEes-----iYDEFVRRSVerakkyvlgnpltpgvsq 342
2H5G_A      251 ICHXYVDSe-----aSVDKVTRLVRDSKCEy-PAACNALETLLIHrdllrtplFDQIIDXLRv----------------- 307
1UXU_A      267 GDPAIVLEd-----aDLDLAADKIARGIYSyaGQRCDAIKLVLAErp-----vYGKLVEEVAkrlsslrvgdprdptvdv 336
1EYY_A      257 INPTFIFPsa---mrAKADLADQFVASMTMgcGQFCTKPGVVFALnt----peTQAFIETAQslirqqspstlltpgird 329
2VRO_B      262 LNSAILCAdatpdtpAFDLFIKEVVREMTVksGQKCTAIRRAFVPea-----aLEPVLEALKaklakitvgnprndavrm 336
gi 74728442 276 ESLLLLTDt-----aDVDSAVEGVVDAAWSd-RGPGGLRLLIQESv-------WDEAMRRLQermgrlrsgrgldgavdm 342
gi 75521601 247 NNPLIIDEv-----aDIDAAVHLTIQSAFVtaGQRCTCARRVLLKsg----aqGDAFLARLVavsqrltpgnwddepqpf 317
gi 91200062 250 KNAIIVLDg-----aNMEIAVNASILSAFKtsGQRCTSAGRLILHvn-----mLEEFEKRFVelakrikignpldeevfm 319
gi 75248520 305 FDWKVLGPdv----qEVDYVAWQCDQDAYAcsGQKCSAQSMLFVHen----wsKTPLVSKLKelaerrkledltigpvlt 376
gi 11072185 319 VNNVVIESt-----dQYKAMLRNLAFTLCLysGQMCTTTQAILVPadgidtdqGRKSYDEVCadlatsidkfladpavat 393
                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                       
1BXS_A      343 gpqidkeqyeki-----ldliesgkkegaklecgggpwgnkgyfiqpTVFSdvtddm-----------riakeEIFGPVQ 406
2H5G_A      308 ----------------------------------------------eQVKIhagpkfasyltfspsevkslrtEYGDLEL 341
1UXU_A      337 gplispsavde-------mmaaiedavekggrvlaggrrlgptyvqpTFVEapadrvk--------dmvlykrEVFAPVA 401
1EYY_A      330 syqsqv------------------vsrgsddgidvtfsqaespcvasALFVtssenwr--------khpaweeEIFGPQS 383
2VRO_B      337 gslvsreqyenvlagiaalreeavlaydssavplidadaniaacvapHLFVvndpdna---------tllhdvEVFGPVA 407
gi 74728442 343 gargaaacdlv-------qrfvreaqsqgaqvfqagdvpserpfyppTLVSnlppas-----------pcaqvEVPWPVV 404
gi 75521601 318 iggliseqaaqqv----ftawqqleamggrtllaprllqagtslltpGIIEmtgva------------gvpdeEVFGPLL 381
gi 91200062 320 gpvinqaatekilr-yndfaknegaevlldgsrltgggydkgyfmspFVYRmknnpk----------srvlheEVFGPHV 388
gi 75248520 377 ftteamlehmenl----lqipgskllfggkelknhsipsiygaleptAVYVpieeilkdn-----ktyelvtkEIFGPFQ 447
gi 11072185 394 avlgaiqspdtla----riaeapahgrvvrastkiehaefpgaevrsPLLLacdaad----------ekaymeERFGPIA 459
                       410       420       430       440       450       460       470       480
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                       
1BXS_A      407 QIMKfk--------slDDVIKRANNTfygLSAGIFTnd--iDKAITVSSal--qsGTVWVNcysvv---------saqcp 465
2H5G_A      342 CIEVvd--------nvQDAIDHIHKYgssHTDVIVTed--eNTAEFFLQhv--dsACVFWNastrfsdgy-rfglgaevg 408
1UXU_A      402 LAVEvk--------dlDQAIELANGRpygLDAAVFGrd--vVKIRRAVRll--evGAIYINdmprhg--------igyyp 461
1EYY_A      384 LIVVce--------nvADMLSLSEMLagsLTATIHAteedyPQVSQLIPrleeiaGRLVFNgwptgve------vgyamv 449
2VRO_B      408 SVAPyrvttdtnalpeAHAVALARRGqgsLVASIYSnd--dAHLGRLALeladshGRVHAIspsvqhsqtghgnvmpmsl 485
gi 74728442 405 VASPfr--------taKEALLVANGTprgGSASVWSer--lGQALELGYgl--qvGTVWINahglr---------dpsvp 463
gi 75521601 382 RVWRyd--------sfEEAIRMANNTrfgLSCGLVSpe--rEKFDQLLLea--raGIVNWNkpltga--------astap 441
gi 91200062 389 AIIPve--------siDEAINVYNDTeygLSCAVITed--fRKARRIRDdc--eyGLGYVNlptiga--------evhlp 448
gi 75248520 448 IVTEykk------dqlPLVLEALERMhahLTAAVVSnd--pIFLQEVIGns--vnGTTYAGlrgrtt--------gapqn 509
gi 11072185 460 FVVKvadg-----aaaVTLSERIVREhgaLTVGLYTtk--pEVVDAMTEatw-raGVALSInltggvfvn--qsagfsdy 529
                       490       500       510
                ....*....|....*....|....*....|..
Feature 1                                       
1BXS_A      466 FGGfkmsgngre---lgeygfheYTEVKTVTI 494
2H5G_A      409 ISTsriharg-------pvglegLLTTKWLLR 433
1UXU_A      462 FGGrkksgvfre---gigyaveaVTAYKTIVF 490
1EYY_A      450 HGGpypasthsastsvgaeaihrWLRPVAYQA 481
2VRO_B      486 HGGpgragggee--lgglralafYHRRSAIQA 515
gi 74728442 464 TGGckesgcswh---ggpdglyeYLRPSGTPA 492
gi 75521601 442 FGGigasgnhr----psawyaadYCAWPMASL 469
gi 91200062 449 FGGlkksgtglp---sastlidaVTHRTAWTV 477
gi 75248520 510 HWFgpagdprgag-igtpeaiklVWSCHREVI 540
gi 11072185 530 HGVgmnpaana----slsdsafvANRFRVVQR 557

| Disclaimer | Privacy statement | Accessibility |
NCBI Home NCBI Search NCBI SiteMap