1nsd
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INFLUENZA B VIRUS NEURAMINIDASE CAN SYNTHESIZE ITS OWN INHIBITOR
OverviewOverview
BACKGROUND: Neuraminidase, one of the two surface glycoproteins of, influenza virus, cleaves terminal sialic acid residues from glycolipids or, glycoproteins. Its crystal structure is known at high resolution, but the, mechanism of glycosyl hydrolysis remains unclear. RESULTS: We have, determined the crystal structure at 1.8 A resolution of two complexes of, influenza B/Beijing neuraminidase containing either the reaction product, sialic acid, or the transition state analogue inhibitor, 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA). The sialic acid is, bound in a distorted 'boat' conformation closely resembling that of bound, DANA, stabilized by a conserved tyrosine residue (Tyr408). This distortion, also gives rise to a suicidal side reaction that converts sialic acid to, DANA at a low rate. CONCLUSIONS: The mechanism of neuraminidase action is, distinct from that of other known glycosyl hydrolases. Substrate, distortion appears to be the driving force in glycosyl bond hydrolysis and, the proton required for catalysis can probably be donated by water, rather, than by residues in the active site, thus allowing the enzyme to operate, at high pH. The side reaction converting sialic acid to DANA appears, reasonably favourable, and it is unclear how this is minimized by the, enzyme.
About this StructureAbout this Structure
1NSD is a Single protein structure of sequence from Influenza b virus with NAG, CA and DAN as ligands. Active as Exo-alpha-sialidase, with EC number 3.2.1.18 Full crystallographic information is available from OCA.
ReferenceReference
Influenza B virus neuraminidase can synthesize its own inhibitor., Burmeister WP, Henrissat B, Bosso C, Cusack S, Ruigrok RW, Structure. 1993 Sep 15;1(1):19-26. PMID:8069621
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