1upa
From Proteopedia
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CARBOXYETHYLARGININE SYNTHASE FROM STREPTOMYCES CLAVULIGERUS (SEMET STRUCTURE)
Overview
The initial step in the biosynthesis of the clinically important, beta-lactamase inhibitor clavulanic acid involves condensation of two, primary metabolites, D-glyceraldehyde 3-phosphate and L-arginine, to give, N2-(2-carboxyethyl)arginine, a beta-amino acid. This unusual N-C bond, forming reaction is catalyzed by the thiamin diphosphate (ThP2)-dependent, enzyme N2-(2-carboxyethyl)arginine synthase. Here we report the crystal, structure of N2-(2-carboxyethyl)arginine synthase, complexed with ThP2 and, Mg2+, to 2.35-A resolution. The structure was solved in two space groups, P2(1)2(1)2(1) and P2(1)2(1)2. In both, the enzyme is observed in a, tetrameric form, composed of a dimer of two more tightly associated, dimers, consistent with both mass spectrometric and gel filtration, chromatography studies. Both ThP2 and Mg2+ cofactors are present at the, active site, with ThP2 in a "V" conformation as in related enzymes. A, sulfate anion is observed in the active site of the enzyme in a location, proposed as a binding site for the phosphate group of the d-glyceraldehyde, 3-phosphate substrate. The mechanistic implications of the active site, arrangement are discussed, including the potential role of the, aminopyrimidine ring of the ThP2. The structure will form a basis for, future mechanistic and structural studies, as well as engineering aimed at, production of alternative beta-amino acids.
About this Structure
1UPA is a Single protein structure of sequence from Streptomyces clavuligerus with , and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Crystal structure and mechanistic implications of N2-(2-carboxyethyl)arginine synthase, the first enzyme in the clavulanic acid biosynthesis pathway., Caines ME, Elkins JM, Hewitson KS, Schofield CJ, J Biol Chem. 2004 Feb 13;279(7):5685-92. Epub 2003 Nov 17. PMID:14623876
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