2xep

Structural and mechanistic studies on a cephalosporin esterase from the clavulanic acid biosynthesis pathway

spinqualitylabelsall models 2xep, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xep is a 2 chain structure with sequence from Streptomyces clavuligerus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.5Å Ligands: CL, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8KRB7_STRCL Publication Abstract from PubMed Structural and biochemical studies of the orf12 gene product (ORF12) from the clavulanic acid (CA) biosynthesis gene cluster are described. Sequence and crystallographic analyses reveal two domains: a C-terminal penicillin-binding protein (PBP)/beta-lactamase-type fold with highest structural similarity to the class A beta-lactamases fused to an N-terminal domain with a fold similar to steroid isomerases and polyketide cyclases. The C-terminal domain of ORF12 did not show beta-lactamase or PBP activity for the substrates tested, but did show low-level esterase activity towards 3'-O-acetyl cephalosporins and a thioester substrate. Mutagenesis studies imply that Ser173, which is present in a conserved SXXK motif, acts as a nucleophile in catalysis, consistent with studies of related esterases, beta-lactamases and D-Ala carboxypeptidases. Structures of wild-type ORF12 and of catalytic residue variants were obtained in complex with and in the absence of clavulanic acid. The role of ORF12 in clavulanic acid biosynthesis is unknown, but it may be involved in the epimerization of (3S,5S)-clavaminic acid to (3R,5R)-clavulanic acid. Structural and mechanistic studies of the orf12 gene product from the clavulanic acid biosynthesis pathway.,Valegard K, Iqbal A, Kershaw NJ, Ivison D, Genereux C, Dubus A, Blikstad C, Demetriades M, Hopkinson RJ, Lloyd AJ, Roper DI, Schofield CJ, Andersson I, McDonough MA Acta Crystallogr D Biol Crystallogr. 2013 Aug;69(Pt 8):1567-79. doi:, 10.1107/S0907444913011013. Epub 2013 Jul 20. PMID:23897479 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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