1q19

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spinqualitylabelsall models 1q19, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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 MG, APC and SSC 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

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