1O7A

Human beta-Hexosaminidase B

Summary for 1O7A

• Entry DOI: 10.2210/pdb1o7a/pdb
• Related: 1QBD
• Descriptor: BETA-HEXOSAMINIDASE BETA CHAIN, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-(acetylamido)-2-deoxy-D-glucono-1,5-lactone, ... (6 entities in total)
• Functional Keywords: hydrolase, glycosyl hydrolase, hexosaminidase, lysosomal, sphingolipid degradation, sandhoff disease, ba8-barrel, glycosidase
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 6
• Total formula weight: 359674.09

Authors

Maier, T.,Strater, N.,Schuette, C.,Klingenstein, R.,Sandhoff, K.,Saenger, W. (deposition date: 2002-10-29, release date: 2003-10-23, Last modification date: 2024-11-13)

Primary citation

Maier, T.,Strater, N.,Schuette, C.,Klingenstein, R.,Sandhoff, K.,Saenger, W.
The X-Ray Crystal Structure of Human Beta-Hexosaminidase B Provides New Insights Into Sandhoff Disease
J.Mol.Biol., 328:669-, 2003

PubMed Abstract: 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.

PubMed: 12706724
DOI: 10.1016/S0022-2836(03)00311-5

Experimental method

X-RAY DIFFRACTION (2.25 Å)