1o7a: Difference between revisions

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.

1O7A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG, GDL and EDO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Beta-N-acetylhexosaminidase Beta-N-acetylhexosaminidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.52 3.2.1.52] Structure known Active Site: ABC. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1O7A OCA].  

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