1lzk
From Proteopedia
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BACTERIAL HEROIN ESTERASE COMPLEX WITH TRANSITION STATE ANALOG DIMETHYLARSENIC ACID
Overview
The crystal structures of an acetyl esterase, HerE, and its complex with, an inhibitor dimethylarsinic acid have been determined at 1.30- and 1.45-A, resolution, respectively. Although the natural substrate for the enzyme is, unknown, HerE hydrolyzes the acetyl groups from heroin to yield morphine, and from phenyl acetate to yield phenol. Recently, the activity of the, enzyme toward heroin has been exploited to develop a heroin biosensor, which affords higher sensitivity than other currently available detection, methods. The crystal structure reveals a single domain with the canonical, alpha/beta hydrolase fold with an acyl binding pocket that snugly, accommodates the acetyl substituent of the substrate and three backbone, amides that form a tripartite oxyanion hole. In addition, a covalent, adduct was observed between the active site serine and dimethylarsinic, acid, which inhibits the enzyme. This crystal structure provides the first, example of an As-containing compound in a serine esterase active site and, the first example of covalent modification of serine by arsenic. Thus, the, HerE complex reveals the structural basis for the broad scope inhibition, of serine hydrolases by As(V)-containing organic compounds.
About this Structure
1LZK is a Single protein structure of sequence from Rhodococcus sp. with CAC as ligand. Full crystallographic information is available from OCA.
Reference
Observation of an arsenic adduct in an acetyl esterase crystal structure., Zhu X, Larsen NA, Basran A, Bruce NC, Wilson IA, J Biol Chem. 2003 Jan 17;278(3):2008-14. Epub 2002 Nov 5. PMID:12421810
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