Conserved Protein Domain Family
GH20_HexA_HexB-like

?
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
?
PSSM-Id: 119332
View PSSM: cd06562
Aligned: 59 rows
Threshold Bit Score: 429.325
Threshold Setting Gi: 145515457
Created: 16-Nov-2005
Updated: 17-Jan-2013
Structure
?
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
?
Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                   #                            #                                       
1NP0_B       151 FSHRGILIDTSRHYLPVKIILKTLDAMAFNKFNVLHWHIVDDQSFPYQSITFPelsnkgsyslshVYTPNDVRMVIEYAR 230
gi 15220590  171 FGHRGVLLDTSRNYYGVDDIMRTIKAMSANKLNVFHWHITDSQSFPLVLPSEPslaakgslgpdmVYTPEDVSKIVQYGF 250
gi 6002489   177 YPHRGIMIDTGRNFITVRKLLEQIDGMALSKLNVLHWHLDDSQSWPMQMSSYPemtkda-yspreIYTEHDMRRVIAYAR 255
gi 50257603  202 FGWRAVLLDTSRHYFSVPSILKILDTMSMVKLNVFHWHVTDSNSWPLDLDSYPelaakgassqseRYSQKDMQMIIDYAG 281
gi 111061715 223 FQHRGINLDVSRNYFSVADIKRQIDALAYNKMNRFHLHITDSQSWPLVIPSLPtlaakgayrpdlVYTPQDFADIQRHAA 302
gi 1839393   211 YPHRGLLLDVSRHWFEVSDIERTIDALAMNKMNVLHLHATDTQSWPLEIPSLPllaekgayhkglSYSPSDLASIQEYGV 290
gi 119193454 213 WSHRGLNLDISRNPIGPNDVKRTIDAMASVKLNRLHIHATDSQSWPLDIPSLPsmaakaayhpglVWSSSDLRNVQKYGL 292
gi 154309489 209 FAHRGLNMDISRNWYPVEDIKRTMLAMHYTKCSVIHLHITDAQSWPLDIPALPelsklgayatglSYTPADLKEIQEYGV 288
gi 190347601 172 YPHRGLMIDSARNYLTVNSILEQIDIMALSKMNTLHWHLVDTQSWPIVLESHPemalda-yssqeVYTRADIQAIVSYGR 250
gi 169857983 179 RMLTSLSFPIADIKRTLDAMSWVKLDTNSWQVNTLHWHIVDAQSFPLVVPGFEelsrkgaynpasIYTPNDVKDIVNYAA 258
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                      #                                                                 
1NP0_B       231 LRGIRVLPEFDTPGHTLSWGKGQkdlltpcys-----------rqnkldsfGPINPTLNTTYSFLTTFFKEISEVFp--d 297
gi 15220590  251 EHGVRVLPEIDTPGHTGSWGEAYpeivtcanmfwwpagksweerlasepgtGQLNPLSPKTYEVVKNVIQDIVNQFp--e 328
gi 6002489   256 ARGVRVIPEVDMPAHSASGWQQVdpeivacaeswwsn-dvwaehtavqpnpGQLDIIYPKTYEVVNNVYQELSRIFs--d 332
gi 50257603  282 HRGIDTLLEIDTPGHTASIAPSHpsfvacfestp-------fkhfahqppaGQLRFADEKVTEWTAQLLREIGSLSk--g 352
gi 111061715 303 IQGVEMITEIDMPGHTASIWHAFpdlisaynkqp------dwstwaaeppsGTLKLNSPAVYDFLNTLLADLLPRVapys 376
gi 1839393   291 HRGVQVIVEIDMPGHVGIDKAYPglsnaygvnp--------wqwycaqppcGSFKLNNTDVEKFIDKLFEDLLPRLspys 362
gi 119193454 293 ARGVSTFIEIDMPGHTGSIGHAFpdlvvafgnds-------wdkyaleppcGQVKLNDSAVRRFFDTVMADILPRVspft 365
gi 154309489 289 ELGIEVILEIDMPGHTSSIGYSHpelmaalfaep-------wdtycaeppcGSLRLNDSAVPAFLEKLFDDLLPRVspys 361
gi 190347601 251 QRAIRIIPEIDMPGHARAGWRRNdaelvicgdtdw-----ekqstavepppGQLNLILNKTYDVVKEVYDEVSSAFs--d 323
gi 169857983 259 QRGIDILVEVDTPGHTSIIHHAHpehiacfeaspw-----tryaygkcillCGLRLASPATVNFTSSLLTSVARLFp--s 331
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1               ##                                                              #        
1NP0_B       298 QFIHLGGDEVEFKCWesnPKIQDFMrqkgf------gtdfKKLESFYIQKVLDIIATin-------kGSIVWQEvfddka 364
gi 15220590  329 SFFHGGGDEVIPGCWktdPAINSFLssg---------gtlSQLLEKYINSTLPYIVSqn-------rTVVYWEDvlldaq 392
gi 6002489   333 NLFHVGADEIQPNCYnysTHITKWFaedp-------srtyNDLAQYWVDHSMPIFRSvgd-----hrRLMMWEDiaiate 400
gi 50257603  353 GYFSTGGDEINMNCMledMPTASKLkakg--------wtlDDALDHFTEKTHAPLRQag-------kTPVVWQEmalnhg 417
gi 111061715 377 SYFHTGGDEVNKNAYtldETVGSNDta-----------ilQPLMQKFVDRNHDQVRAag-------lTPLVWEEmllewn 438
gi 1839393   363 AYFHTGGDEYKANNSlldPALRTNDmn-----------tlQPMLQRFLDHVHGKVRDlg-------lVPMVWEEmildwn 424
gi 119193454 366 AYFHTGGDEFNLQSYmleETIRSNDpk-----------vlKPLLQDFVNRVHMQIMEag-------lTPIVWEElvldwd 427
gi 154309489 362 SYFHTGGDEVNVNTYlldPTVQSNDta-----------vlTPLIQAFVDRNHKQVRAag-------lTPMVWEEmittwn 423
gi 190347601 324 NLFHVGSDEVSVGCYnssLSIRTWLeshs-------krgfSGLIDHWLDEALPIFKNkk------arRLIMWEDvllssv 390
gi 169857983 332 KFFSTGGDEINQPCYeddAATQKELdpdylglvekqgktlEQALDTFTQVTHRALHDmgkttvvwqgMSHTYSYdrvens 411
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                              #                           # #                           
1NP0_B       365 ------------klapgTIVEVWKDsaypeeLSRVTASGFPVILSa--pWYLDLIsyg---------------------- 408
gi 15220590  393 ika-----dpsvlpkehTILQTWNNgp--enTKRIVAAGYRVIVSssefYYLDCGhggflgndsi-----------ydqk 454
gi 6002489   401 s---------ahdvpkdVIMQTWNSgegegnIKKLTSAGYDVVVStsdfLYLDCGrggyvtndarynvqsntdggvnfny 471
gi 50257603  418 t---------mssltndTIVDIWVNsa---dARKVLDQGYRIVHAsadyFYLDCGqggwige------------------ 467
gi 111061715 439 -----------vtlgsdVIVQSWQSdq---aVKDIVDKGHKVLVGnynyWYLDCGkgqfldfaps-----------saag 493
gi 1839393   425 -----------atlgkdVVAQTWLGgg---aIQKLAQAGYKVIDSsndfYYLDCGrgewldfangd----------pfnn 480
gi 119193454 428 ltf-----psqqsetqgIIVQAWRNst---aVRQILEKGYRTIFGsgdaWYLDCGvggfinprpg-----------sgav 488
gi 154309489 424 -----------ltlgsdVLVQSWLSda---sVAQIVAAGHKAIAGnynfWYLDCGkgqwlnfepga----------ssek 479
gi 190347601 391 n---------asnlpkdVILQSWREht---nIQQLASRGYDVIISsssfLYLDCGvgtfftndiryven----vtnynwn 454
gi 169857983 412 ssavemvldhkvtlsndTVAMVWISsq---hAKAVAQRGHRLIHAasdyFYLDCGgggwign------------------ 470
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                  # #                                   
1NP0_B       409 ----qdWRKYYKVEPLdfggtq-------kqkqlFIGGEACLWGEYVDATNLTPRLWPRASAVGERLWSskdvrd----- 472
gi 15220590  455 esgggsWCAPFKTWQSiynydiadgllneeerklVLGGEVALWSEQADSTVLDSRLWPRASALAESLWSgnrdergv--k 532
gi 6002489   472 ggdggsWCAPYKTWQRiydydfltn-ltsseakhIIGAEAPLWSEQVDDVTVSSVFWPRAAALGELVWSgnrdaagr--k 548
gi 50257603  468 eggnnsWCDPMKSWARmysfdpfkd-vkdeerhlVLGGQTSLWTEQTDETNLEPTLWPRAAALAEVFWSgpgqdsrp--r 544
gi 111061715 494 fwpyndYCAPFHNWRLiysydplag-ipadkqhlVLGGEAHMWAEMTDPVNVDRMVWPRAAAVGEILWSgakdemgqn-r 571
gi 1839393   481 nypfldWCDPTKNWKLmysheptdg-vsddlkknVIGGEVAVWTETIDPTSLDSIIWPRAGAAAEIWWSgkidekgqn-r 558
gi 119193454 489 kepyldWCSPTKNWRHiytynpleg-ipeelqslLEGGETHMWAENVDPVNMDQMIWPRAASAAEVLWSgprardd---- 563
gi 154309489 480 yfpyndYCSPTKSWRLvysydplag-vpensthlVVGGEFHIWSEQTDPINLDDMVWPRGAAAAEVLWSgakdpvtgqnr 558
gi 190347601 455 yngrdsWCGPYKTWQRiysmnitgs-ltetekshILGYEAPLWSEQVDSNILTQKLWPRAAALAELSWSgnlnekgq--l 531
gi 169857983 471 npngnsWCDPFKTWQKaysfnpran-lteeeaklVLGGQQLLWAEQSGPSNLDPIVWPRAAASAEVFWSghgrdg----- 544
                        410       420
                 ....*....|....*....|
Feature 1                            
1NP0_B       473 -mddaydRLTRHRCRMVERG 491
gi 15220590  533 rcgeavdRLNLWRYRMVKRG 552
gi 6002489   549 rttsftqRILNFREYLVANG 568
gi 50257603  545 ssnkalpRMHDIRYRMVGRG 564
gi 111061715 572 sqidaspRLGEMRERLVARG 591
gi 1839393   559 sqidarpRLSEQRERMLARG 578
gi 119193454 564 -imeashRLGKWRERAVIDM 582
gi 154309489 559 sqidagsRLPEFNEHLRSLG 578
gi 190347601 532 rledfgqRLLAFREYLVSLG 551
gi 169857983 545 --rtalpRLHDLAYRFVQRG 562

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