1NP0,2GK1,2GK1


Conserved Protein Domain Family
GH20_HexA_HexB-like

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cd06562: GH20_HexA_HexB-like 
Click on image for an interactive view with Cn3D
Beta-N-acetylhexosaminidases catalyze the removal of beta-1,4-linked N-acetyl-D-hexosamine residues from the non-reducing ends of N-acetyl-beta-D-hexosaminides including N-acetylglucosides and N-acetylgalactosides. The hexA and hexB genes encode the alpha- and beta-subunits of the two major beta-N-acetylhexosaminidase isoenzymes, N-acetyl-beta-D-hexosaminidase A (HexA) and beta-N-acetylhexosaminidase B (HexB). Both the alpha and the beta catalytic subunits have a TIM-barrel fold and belong to the glycosyl hydrolase family 20 (GH20). The HexA enzyme is a heterodimer containing one alpha and one beta subunit while the HexB enzyme is a homodimer containing two beta-subunits. Hexosaminidase mutations cause an inability to properly hydrolyze certain sphingolipids which accumulate in lysosomes within the brain, resulting in the lipid storage disorders Tay-Sachs and Sandhoff. Mutations in the alpha subunit cause in a deficiency in the HexA enzyme and result in Tay-Sachs, mutations in the beta-subunit cause in a deficiency in both HexA and HexB enzymes and result in Sandhoff disease. In both disorders GM(2) gangliosides accumulate in lysosomes. The GH20 hexosaminidases are thought to act via a catalytic mechanism in which the catalytic nucleophile is not provided by solvent or the enzyme, but by the substrate itself.
Statistics
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PSSM-Id: 119332
View PSSM: cd06562
Aligned: 59 rows
Threshold Bit Score: 429.325
Threshold Setting Gi: 145515457
Created: 16-Nov-2005
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
active site
Conserved site includes 11 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Structure:1NP0_A; Homo sapiens Lysosomal Beta-Hexosaminidase isoform B (HexB) beta subunit, binds an intermediate analog NAG-Thiazoline (N-acetyl-beta-D-glucosamine-thiazoline).
    View structure with Cn3D
  • Structure:2GK1_A/B; Homo sapiens Lysosomal Beta-Hexosaminidase isoform A (HexA), alpha and beta subunits each bind an intermediate analog NAG-Thiazoline (N-acetyl-beta-D-glucosamine-thiazoline), contacts at 4 A.
    View structure with Cn3D
  • Comment:there are two active sites in the HexA heterodimer, one in the alpha subunit, one in the beta subunit. A Tyr residue from the beta subunit is found in the active site of the alpha subunit and vice versa.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                   #                            #                                       
1NP0_B       151 FSHRGILIDTSRHYLPVKIILKTLDAMAFNKFNVLHWHIVDDQSFPYQSITFPelsnkgsyslshVYTPNDVRMVIEYAR 230 human
NP_172050    171 FGHRGVLLDTSRNYYGVDDIMRTIKAMSANKLNVFHWHITDSQSFPLVLPSEPslaakgslgpdmVYTPEDVSKIVQYGF 250 thale cress
AAF00010     177 YPHRGIMIDTGRNFITVRKLLEQIDGMALSKLNVLHWHLDDSQSWPMQMSSYPemtkda-yspreIYTEHDMRRVIAYAR 255 Penicillium chr...
EAL20308     202 FGWRAVLLDTSRHYFSVPSILKILDTMSMVKLNVFHWHVTDSNSWPLDLDSYPelaakgassqseRYSQKDMQMIIDYAG 281 Cryptococcus ne...
EAT82835     223 FQHRGINLDVSRNYFSVADIKRQIDALAYNKMNRFHLHITDSQSWPLVIPSLPtlaakgayrpdlVYTPQDFADIQRHAA 302 Phaeosphaeria n...
AAB47061     211 YPHRGLLLDVSRHWFEVSDIERTIDALAMNKMNVLHLHATDTQSWPLEIPSLPllaekgayhkglSYSPSDLASIQEYGV 290 Hypocrea lixii
XP_001247333 213 WSHRGLNLDISRNPIGPNDVKRTIDAMASVKLNRLHIHATDSQSWPLDIPSLPsmaakaayhpglVWSSSDLRNVQKYGL 292 Coccidioides im...
XP_001554078 209 FAHRGLNMDISRNWYPVEDIKRTMLAMHYTKCSVIHLHITDAQSWPLDIPALPelsklgayatglSYTPADLKEIQEYGV 288 Botryotinia fuc...
EDK39905     172 YPHRGLMIDSARNYLTVNSILEQIDIMALSKMNTLHWHLVDTQSWPIVLESHPemalda-yssqeVYTRADIQAIVSYGR 250 Pichia guillier...
XP_001835638 179 RMLTSLSFPIADIKRTLDAMSWVKLDTNSWQVNTLHWHIVDAQSFPLVVPGFEelsrkgaynpasIYTPNDVKDIVNYAA 258 Coprinopsis cin...
Feature 1                      #                                                                 
1NP0_B       231 LRGIRVLPEFDTPGHTLSWGKGQkdlltpcys-----------rqnkldsfGPINPTLNTTYSFLTTFFKEISEVFp--d 297 human
NP_172050    251 EHGVRVLPEIDTPGHTGSWGEAYpeivtcanmfwwpagksweerlasepgtGQLNPLSPKTYEVVKNVIQDIVNQFp--e 328 thale cress
AAF00010     256 ARGVRVIPEVDMPAHSASGWQQVdpeivacaeswwsn-dvwaehtavqpnpGQLDIIYPKTYEVVNNVYQELSRIFs--d 332 Penicillium chr...
EAL20308     282 HRGIDTLLEIDTPGHTASIAPSHpsfvacfestp-------fkhfahqppaGQLRFADEKVTEWTAQLLREIGSLSk--g 352 Cryptococcus ne...
EAT82835     303 IQGVEMITEIDMPGHTASIWHAFpdlisaynkqp------dwstwaaeppsGTLKLNSPAVYDFLNTLLADLLPRVapys 376 Phaeosphaeria n...
AAB47061     291 HRGVQVIVEIDMPGHVGIDKAYPglsnaygvnp--------wqwycaqppcGSFKLNNTDVEKFIDKLFEDLLPRLspys 362 Hypocrea lixii
XP_001247333 293 ARGVSTFIEIDMPGHTGSIGHAFpdlvvafgnds-------wdkyaleppcGQVKLNDSAVRRFFDTVMADILPRVspft 365 Coccidioides im...
XP_001554078 289 ELGIEVILEIDMPGHTSSIGYSHpelmaalfaep-------wdtycaeppcGSLRLNDSAVPAFLEKLFDDLLPRVspys 361 Botryotinia fuc...
EDK39905     251 QRAIRIIPEIDMPGHARAGWRRNdaelvicgdtdw-----ekqstavepppGQLNLILNKTYDVVKEVYDEVSSAFs--d 323 Pichia guillier...
XP_001835638 259 QRGIDILVEVDTPGHTSIIHHAHpehiacfeaspw-----tryaygkcillCGLRLASPATVNFTSSLLTSVARLFp--s 331 Coprinopsis cin...
Feature 1               ##                                                              #        
1NP0_B       298 QFIHLGGDEVEFKCWesnPKIQDFMrqkgf------gtdfKKLESFYIQKVLDIIATin-------kGSIVWQEvfddka 364 human
NP_172050    329 SFFHGGGDEVIPGCWktdPAINSFLssg---------gtlSQLLEKYINSTLPYIVSqn-------rTVVYWEDvlldaq 392 thale cress
AAF00010     333 NLFHVGADEIQPNCYnysTHITKWFaedp-------srtyNDLAQYWVDHSMPIFRSvgd-----hrRLMMWEDiaiate 400 Penicillium chr...
EAL20308     353 GYFSTGGDEINMNCMledMPTASKLkakg--------wtlDDALDHFTEKTHAPLRQag-------kTPVVWQEmalnhg 417 Cryptococcus ne...
EAT82835     377 SYFHTGGDEVNKNAYtldETVGSNDta-----------ilQPLMQKFVDRNHDQVRAag-------lTPLVWEEmllewn 438 Phaeosphaeria n...
AAB47061     363 AYFHTGGDEYKANNSlldPALRTNDmn-----------tlQPMLQRFLDHVHGKVRDlg-------lVPMVWEEmildwn 424 Hypocrea lixii
XP_001247333 366 AYFHTGGDEFNLQSYmleETIRSNDpk-----------vlKPLLQDFVNRVHMQIMEag-------lTPIVWEElvldwd 427 Coccidioides im...
XP_001554078 362 SYFHTGGDEVNVNTYlldPTVQSNDta-----------vlTPLIQAFVDRNHKQVRAag-------lTPMVWEEmittwn 423 Botryotinia fuc...
EDK39905     324 NLFHVGSDEVSVGCYnssLSIRTWLeshs-------krgfSGLIDHWLDEALPIFKNkk------arRLIMWEDvllssv 390 Pichia guillier...
XP_001835638 332 KFFSTGGDEINQPCYeddAATQKELdpdylglvekqgktlEQALDTFTQVTHRALHDmgkttvvwqgMSHTYSYdrvens 411 Coprinopsis cin...
Feature 1                              #                           # #                           
1NP0_B       365 ------------klapgTIVEVWKDsaypeeLSRVTASGFPVILSa--pWYLDLIsyg---------------------- 408 human
NP_172050    393 ika-----dpsvlpkehTILQTWNNgp--enTKRIVAAGYRVIVSssefYYLDCGhggflgndsi-----------ydqk 454 thale cress
AAF00010     401 s---------ahdvpkdVIMQTWNSgegegnIKKLTSAGYDVVVStsdfLYLDCGrggyvtndarynvqsntdggvnfny 471 Penicillium chr...
EAL20308     418 t---------mssltndTIVDIWVNsa---dARKVLDQGYRIVHAsadyFYLDCGqggwige------------------ 467 Cryptococcus ne...
EAT82835     439 -----------vtlgsdVIVQSWQSdq---aVKDIVDKGHKVLVGnynyWYLDCGkgqfldfaps-----------saag 493 Phaeosphaeria n...
AAB47061     425 -----------atlgkdVVAQTWLGgg---aIQKLAQAGYKVIDSsndfYYLDCGrgewldfangd----------pfnn 480 Hypocrea lixii
XP_001247333 428 ltf-----psqqsetqgIIVQAWRNst---aVRQILEKGYRTIFGsgdaWYLDCGvggfinprpg-----------sgav 488 Coccidioides im...
XP_001554078 424 -----------ltlgsdVLVQSWLSda---sVAQIVAAGHKAIAGnynfWYLDCGkgqwlnfepga----------ssek 479 Botryotinia fuc...
EDK39905     391 n---------asnlpkdVILQSWREht---nIQQLASRGYDVIISsssfLYLDCGvgtfftndiryven----vtnynwn 454 Pichia guillier...
XP_001835638 412 ssavemvldhkvtlsndTVAMVWISsq---hAKAVAQRGHRLIHAasdyFYLDCGgggwign------------------ 470 Coprinopsis cin...
Feature 1                                                  # #                                   
1NP0_B       409 ----qdWRKYYKVEPLdfggtq-------kqkqlFIGGEACLWGEYVDATNLTPRLWPRASAVGERLWSskdvrd----- 472 human
NP_172050    455 esgggsWCAPFKTWQSiynydiadgllneeerklVLGGEVALWSEQADSTVLDSRLWPRASALAESLWSgnrdergv--k 532 thale cress
AAF00010     472 ggdggsWCAPYKTWQRiydydfltn-ltsseakhIIGAEAPLWSEQVDDVTVSSVFWPRAAALGELVWSgnrdaagr--k 548 Penicillium chr...
EAL20308     468 eggnnsWCDPMKSWARmysfdpfkd-vkdeerhlVLGGQTSLWTEQTDETNLEPTLWPRAAALAEVFWSgpgqdsrp--r 544 Cryptococcus ne...
EAT82835     494 fwpyndYCAPFHNWRLiysydplag-ipadkqhlVLGGEAHMWAEMTDPVNVDRMVWPRAAAVGEILWSgakdemgqn-r 571 Phaeosphaeria n...
AAB47061     481 nypfldWCDPTKNWKLmysheptdg-vsddlkknVIGGEVAVWTETIDPTSLDSIIWPRAGAAAEIWWSgkidekgqn-r 558 Hypocrea lixii
XP_001247333 489 kepyldWCSPTKNWRHiytynpleg-ipeelqslLEGGETHMWAENVDPVNMDQMIWPRAASAAEVLWSgprardd---- 563 Coccidioides im...
XP_001554078 480 yfpyndYCSPTKSWRLvysydplag-vpensthlVVGGEFHIWSEQTDPINLDDMVWPRGAAAAEVLWSgakdpvtgqnr 558 Botryotinia fuc...
EDK39905     455 yngrdsWCGPYKTWQRiysmnitgs-ltetekshILGYEAPLWSEQVDSNILTQKLWPRAAALAELSWSgnlnekgq--l 531 Pichia guillier...
XP_001835638 471 npngnsWCDPFKTWQKaysfnpran-lteeeaklVLGGQQLLWAEQSGPSNLDPIVWPRAAASAEVFWSghgrdg----- 544 Coprinopsis cin...
Feature 1                            
1NP0_B       473 -mddaydRLTRHRCRMVERG 491 human
NP_172050    533 rcgeavdRLNLWRYRMVKRG 552 thale cress
AAF00010     549 rttsftqRILNFREYLVANG 568 Penicillium chrysogenum
EAL20308     545 ssnkalpRMHDIRYRMVGRG 564 Cryptococcus neoformans var. neoformans B-3501A
EAT82835     572 sqidaspRLGEMRERLVARG 591 Phaeosphaeria nodorum SN15
AAB47061     559 sqidarpRLSEQRERMLARG 578 Hypocrea lixii
XP_001247333 564 -imeashRLGKWRERAVIDM 582 Coccidioides immitis RS
XP_001554078 559 sqidagsRLPEFNEHLRSLG 578 Botryotinia fuckeliana B05.10
EDK39905     532 rledfgqRLLAFREYLVSLG 551 Pichia guilliermondii ATCC 6260
XP_001835638 545 --rtalpRLHDLAYRFVQRG 562 Coprinopsis cinerea okayama7#130

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