Beta-Hexosaminidase

spinqualitylabelsall models Humanβ-hexosaminidase (PDB code 2gjx) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structure of Human β-Hexosaminidase A and its association with Tay-Sachs disease β-Hexosaminidase A is a lysosomal enzyme essential for the degradation of GM2 gangliosides. Deficiency of lysosomal β-Hexosaminidase A due to inherited defects in the α-subunit gene results in Tay-Sachs (TS) disease. The 3D structure of β-Hexosaminidase A was determined by the group of Michael N.G. James at the University of Alberta, Edmonton, Canada. The structure reveals an αβ-heterodimer, with each subunit having a functional active site. Only the α-subunit active site can hydrolyze GM2 gangliosides due to a flexible loop α280GSEP283 structure that is removed post-translationaly from β, and to the presence of α-Asn 423 and α-Arg 424. The loop structure is involved in binding the GM2 activator protein, while α-Arg424 is critical for binding the carboxylate group of the N-acetyl-neuraminic acid residue of GM2. Two active sites are present in the HexA dimer; one comprising residues from the α-subunit (R178 D207 H262 E323 D322 W373 W392 W460 Y421 R424 N423 E462) and a second one from residues of the β-subunit (R211 D240 H294 E355 D354 W405 W424 Y450 L453 D452 E491 W489). These active sites are located at the opening of TIM barrels at the interface between the α and β-subunits. The HexA undergoes glycosylation on the α and β-subunits; α-Asn 115, α-Asn 157 and α-Asn 295 β-Asn 84, β-Asn 142, β-Asn 190 and β-Asn 327. Mutations in the α-subunit are associated with TS disease and with Late Onset Tay Sachs disease (LOTS) (Chronic & Acute clinical phenotype). Interestingly, α-G269S is the most common mutation associated with LOTS disease. See also Beta-N-acetylhexosaminidase and Hexosaminidase (Hebrew). 3D Structures of Beta-Hexosaminidase Beta-Hexosaminidase 3D structures

3D Structures of Beta-Hexosaminidase

Updated on 04-August-2022

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• Beta-hexosaminidase
  • Beta-N-acetylhexosaminidase - hBHEXA α+β subunits - human
    
  • Hexosaminidase (Hebrew), Beta-Hexosaminidase 3D structures, 1nou, 1o7a – hBHEXB β subunit
    
  • 5bro - hBHEXB β subunit (mutant)
    
  • 2xpk, 2w1n – CpBHEXB – Clostridium perfringens
    
  • 2o4e – CpBHEXB - NMR
    
  • 2v5c, 2v5d – CpBHEXB catalytic domain
    
  • 2jh2 – CpBHEXB cohesin-like module
    
  • 3gh4 – PaBHEX – Paenibacillus
    
  • 3bmx – BHEX – Bacillus subtilis
    
  • 1tr9 – VcBHEX – Vibrio cholerae
    
  • 1hp4 – SpBHEX – Streptomyces plicatus
    
  • 2ltj – SpnBHEX G5 domain – Streptococcus pneumoniae – NMR
    
  • 2yl5 – SpnBHEX residues 627-1064
    
  • 2yl6, 2yll, 3rpm – SpnBHEX catalytic domain
    
  • 1qba – SmBHEX – Serratia marcescens
    
  • 3nsm – OfBHEX residues 23-594 – Ostrinia furnacalis
    
  • 4ais, 6q63 – BtBHEXB – Bacteroides thetaiotaomicron
    
  • 4g6c – BcBHEX – Burkholderia cenocepacia
    
  • 4gvg - SeBHEX – Salmonella enterica
    
  • 3rcn – BHEX – Arthrobacter aurescens
    
  • 5g1m, 5g2m - PaBHEXB – Pseudomonas aeruginosa
    
  • 5g5u, 5g6t - PaBHEXB (mutant)
    
  • 5oar - BHEXB – yellow mold
    
  • 6jti, 6jtl – NgBHEX – Neisseria gonorrhoeae
    
• Beta-hexosaminidase binary complexes
  • 2gk1 - hBHEXA α+β subunits + NGT
    
  • 1now - hBHEXB β subunit + GalNAc-isofagomine
    
  • 1np0 - hBHEXB β subunit + intermediate analog
    
  • 3gh5, 3gh7 - PaBHEX + GlcNAc
    
  • 4gvf, 4gvh, 4gvi - SeBHEX + GlcNAc derivative
    
  • 4hzm – SeBHEX + inhibitor
    
  • 1m01 - SpBHEX + GlcNAc
    
  • 1m03, 1m04 - SpBHEX (mutant) + GlcNAc
    
  • 1jak - SpBHEX + inhibitor
    
  • 1hp5 - SpBHEX + intermediate analog
    
  • 2x0y, 2wb5, 2vur - CpBHEXB + inhibitor
    
  • 2ozn – CpBHEXB + hyaluronidase
    
  • 3ozo – OfBHEX residues 23-594 + NGT
    
  • 3ozp – OfBHEX residues 23-594 + PUGNac
    
  • 3nsn - OfBHEX residues 23-594 + chitotriomycin
    
  • 3wmb, 3wmc - OfBHEX + inhibitor
    
  • 5y0v - OfBHEX + berberine
    
  • 5y1b - OfBHEX (mutant) + berberine derivative
    
  • 2xj7 – BtBHEXB + castanospermine
    
  • 2wzh, 2wzi - BtBHEXB (mutant) + oxazoline
    
  • 2vvn - BtBHEX + thiazoline
    
  • 2x0h - BtBHEXB Michaelis complex
    
  • 2wca, 2vvs - BtBHEX + PUGNAc
    
  • 2xm1, 2xm2 - BtBHEXB + lactam derivative
    
  • 4aiu - BtBHEXB + pyrazole derivative
    
  • 2w66, 2w67, 2w4x, 2jiw – BtBHEXB + inhibitor
    
  • 3gs6, 3gsm, 2oxn - VcBHEX + PUGNAc
    
  • 1y65 - VcBHEX + NAG
    
  • 4gnv - BcBHEX + NAG
    
  • 4mss, 5utr – BcBHEX + inhibitor
    
  • 6dte – BcBHEX + cyclophellitol
    
  • 5utp, 5utq – BcBHEX + PUGNAc
    
  • 2yl8 – SpnBHEX catalytic domain (mutant) + NAG
    
  • 4az5, 4az6, 4az7, 4az8, 4azc, 4azg, 4azh – SpnBHEX catalytic domain + inhibitor
    
  • 4azi – SpnBHEX catalytic domain (mutant) + inhibitor
    
  • 2yl9, 2yla – SpnBHEX residues 627-1062 (mutant) + NAG
    
  • 1c7s – SmBHEX + diNAG
    
  • 1c7t - SmBHEX (mutant) + diNAG
    
  • 3sur - PaBHEX + NAG derivative
    
  • 3sus - PaBHEX + GAL-NAG derivative
    
  • 3sut - PaBHEX + PUGNac
    
  • 3suu - PaBHEX + GAL-PUGNac
    
  • 3suv - PaBHEX + NHAC-DNJ
    
  • 3suw - PaBHEX + NHAC-CAS
    
  • 5g5k - PaBHEX + jirimycin derivative
    
  • 5ly7 - PaBHEX (mutant) + jirimycin derivative
    
  • 6jtk – Ng BHEX + Glc derivative
    
  • 6jtj – Ng BHEX + NAG derivative
    

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