1q19
From Proteopedia
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Carbapenam Synthetase
Overview
Carbapenam synthetase (CarA) is an ATP/Mg2+-dependent enzyme that catalyzes formation of the beta-lactam ring in (5R)-carbapenem-3-carboxylic acid biosynthesis. CarA is homologous to beta-lactam synthetase (beta-LS), which is involved in clavulanic acid biosynthesis. The catalytic cycles of CarA and beta-LS mediate substrate adenylation followed by beta-lactamization via a tetrahedral intermediate or transition state. Another member of this family of ATP/Mg2+-dependent enzymes, asparagine synthetase (AS-B), catalyzes intermolecular, rather than intramolecular, amide bond formation in asparagine biosynthesis. The crystal structures of apo-CarA and CarA complexed with the substrate (2S,5S)-5-carboxymethylproline (CMPr), ATP analog alpha,beta-methyleneadenosine 5'-triphosphate (AMP-CPP), and a single Mg2+ ion have been determined. CarA forms a tetramer. Each monomer resembles beta-LS and AS-B in overall fold, but key differences are observed. The N-terminal domain lacks the glutaminase active site found in AS-B, and an extended loop region not observed in beta-LS or AS-B is present. Comparison of the C-terminal synthetase active site to that in beta-LS reveals that the ATP binding site is highly conserved. By contrast, variations in the substrate binding pocket reflect the different substrates of the two enzymes. The Mg2+ coordination is also different. Several key residues in the active site are conserved between CarA and beta-LS, supporting proposed roles in beta-lactam formation. These data provide further insight into the structures of this class of enzymes and suggest that CarA might be a versatile target for protein engineering experiments aimed at developing improved production methods and new carbapenem antibiotics.
About this Structure
1Q19 is a Single protein structure of sequence from Pectobacterium carotovorum with , and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure of carbapenam synthetase (CarA)., Miller MT, Gerratana B, Stapon A, Townsend CA, Rosenzweig AC, J Biol Chem. 2003 Oct 17;278(42):40996-1002. Epub 2003 Jul 30. PMID:12890666
Page seeded by OCA on Thu Feb 21 14:34:53 2008
Categories: Pectobacterium carotovorum | Single protein | Gerratana, B. | Miller, M T. | Rosenzweig, A C. | Stapon, A. | Townsend, C A. | APC | MG | SSC | (2s | 5s)-5-carboxymethylproline; b-ls | A | B-lactam synthetase; as-b | B-methyleneadenosine 5-triphosphate; cea | Class b asparagine synthetase; amp-cpp | Cmpr | N2-(carboxyethyl)-l-arginine; cma | N2-(carboxylmethyl)-l-arginine
