1o7a

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spinqualitylabelsall models 1o7a, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

HUMAN BETA-HEXOSAMINIDASE B

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Sandhoff disease, infantile, juvenile, and adult forms OMIM:[606873], Spinal muscular atrophy, juvenile OMIM:[606873]

About this Structure

1O7A is a Single protein structure of sequence from Homo sapiens with NAG, GDL and EDO as ligands. Active as Beta-N-acetylhexosaminidase, with EC number 3.2.1.52 Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

The X-ray crystal structure of human beta-hexosaminidase B provides new insights into Sandhoff disease., Maier T, Strater N, Schuette CG, Klingenstein R, Sandhoff K, Saenger W, J Mol Biol. 2003 May 2;328(3):669-81. PMID:12706724

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