1nx8

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1nx8, resolution 2.30Å

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Structure of carbapenem synthase (CarC) complexed with N-acetyl proline

Overview

The proposed biosynthetic pathway to the carbapenem antibiotics proceeds, via epimerization/desaturation of a carbapenam in an unusual process, catalyzed by an iron- and 2-oxoglutarate-dependent oxygenase, CarC., Crystal structures of CarC complexed with Fe(II) and 2-oxoglutarate reveal, it to be hexameric (space group C2221), consistent with solution studies., CarC monomers contain a double-stranded beta-helix core that supports, ligands binding a single Fe(II) to which 2-oxoglutarate complexes in a, bi-dentate manner. A structure was obtained with l-N-acetylproline acting, as a substrate analogue. Quantum mechanical/molecular mechanical modeling, studies with stereoisomers of carbapenams and carbapenems were used to, investigate substrate binding. The combined work will stimulate further, mechanistic studies and aid in the engineering of carbapenem biosynthesis.

About this Structure

1NX8 is a Single protein structure of sequence from Pectobacterium carotovorum with FE, AKG and N7P as ligands. Full crystallographic information is available from OCA.

Reference

Crystal structure of carbapenem synthase (CarC)., Clifton IJ, Doan LX, Sleeman MC, Topf M, Suzuki H, Wilmouth RC, Schofield CJ, J Biol Chem. 2003 Jun 6;278(23):20843-50. Epub 2003 Feb 28. PMID:12611886

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