2d5j
From Proteopedia
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Unsaturated Glucuronyl Hydrolase Triggers Hydration of Vinyl Ether Group but not of Glycosidic Bond
Overview
Unsaturated glucuronyl hydrolase (UGL), which is a member of glycoside, hydrolase family GH-88, is a bacterial enzyme that degrades mammalian, glycosaminoglycans and bacterial biofilms. The enzyme, which acts on, unsaturated oligosaccharides with an alpha-glycoside bond produced by, microbial polysaccharide lyases responsible for bacterial invasion of host, cells, was believed to release 4-deoxy-l-threo-5-hexosulose-uronate, (unsaturated glucuronic acid, or DeltaGlcA) and saccharide with a new, nonreducing terminus by hydrolyzing the glycosidic bond. We detail the, crystal structures of wild-type inactive mutant UGL of Bacillus sp. GL1, and its complex with a substrate (unsaturated chondroitin disaccharide), identify active site residues, and postulate a reaction mechanism, catalyzed by UGL that triggers the hydration of the vinyl ether group in, DeltaGlcA, based on the structural analysis of the enzyme-substrate, complex and biochemical analysis. The proposed catalytic mechanism of UGL, is a novel case among known glycosidases. Under the proposed mechanism, Asp-149 acts as a general acid and base catalyst to protonate the, DeltaGlcA C4 atom and to deprotonate the water molecule. The deprotonated, water molecule attacks the DeltaGlcA C5 atom to yield unstable hemiketal;, this is followed by spontaneous conversion to an aldehyde, (4-deoxy-l-threo-5-hexosulose-uronate) and saccharide through hemiacetal, formation and cleavage of the glycosidic bond. UGL is the first clarified, alpha(6)/alpha(6)-barrel enzyme using aspartic acid as the general, acid/base catalyst.
About this Structure
2D5J is a Single protein structure of sequence from Bacillus sp.. Full crystallographic information is available from OCA.
Reference
Crystal structure of unsaturated glucuronyl hydrolase complexed with substrate: molecular insights into its catalytic reaction mechanism., Itoh T, Hashimoto W, Mikami B, Murata K, J Biol Chem. 2006 Oct 6;281(40):29807-16. Epub 2006 Aug 7. PMID:16893885
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