1O7A: Human Beta-hexosaminidase B

Human lysosomal beta-hexosaminidases are dimeric enzymes composed of alpha and beta-chains, encoded by the genes HEXA and HEXB. They occur in three isoforms, the homodimeric hexosaminidases B (betabeta) and S (alphaalpha), and the heterodimeric hexosaminidase A (alphabeta), where dimerization is required for catalytic activity. Allelic variations in the HEXA and HEXB genes cause the fatal inborn errors of metabolism Tay-Sachs disease and Sandhoff disease, respectively. Here, we present the crystal structure of a complex of human beta-hexosaminidase B with a transition state analogue inhibitor at 2.3A resolution (pdb 1o7a). On the basis of this structure and previous studies on related enzymes, a retaining double-displacement mechanism for glycosyl hydrolysis by beta-hexosaminidase B is proposed. In the dimer structure, which is derived from an analysis of crystal packing, most of the mutations causing late-onset Sandhoff disease reside near the dimer interface and are proposed to interfere with correct dimer formation. The structure reported here is a valid template also for the dimeric structures of beta-hexosaminidase A and S.
PDB ID: 1O7ADownload
MMDB ID: 24989
PDB Deposition Date: 2002/10/29
Updated in MMDB: 2003/11 
Experimental Method:
x-ray diffraction
Resolution: 2.25  Å
Source Organism:
Similar Structures:
Biological Unit for 1O7A: dimeric; determined by author and by software (PQS)
Molecular Components in 1O7A
Label Count Molecule
Proteins (2 molecules)
Beta-hexosaminidase Beta Chain
Molecule annotation
Chemicals (13 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB