1dcs

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spinqualitylabelsall models 1dcs, resolution 1.3Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

DEACETOXYCEPHALOSPORIN C SYNTHASE FROM S. CLAVULIGERUS

Overview

Penicillins and cephalosporins are among the most widely used therapeutic, agents. These antibiotics are produced from fermentation-derived materials, as their chemical synthesis is not commercially viable. Unconventional, steps in their biosynthesis are catalysed by Fe(II)-dependent, oxidases/oxygenases; isopenicillin N synthase (IPNS) creates in one step, the bicyclic nucleus of penicillins, and deacetoxycephalosporin C synthase, (DAOCS) catalyses the expansion of the penicillin nucleus into the nucleus, of cephalosporins. Both enzymes use dioxygen-derived ferryl intermediates, in catalysis but, in contrast to IPNS, the ferryl form of DAOCS is, produced by the oxidative splitting of a co-substrate, 2-oxoglutarate, (alpha-ketoglutarate). This route of controlled ferryl formation and, reaction is common to many mononuclear ferrous enzymes, which participate, in a broader range of reactions than their well-characterized, counterparts, the haem enzymes. Here we report the first crystal structure, of a 2-oxoacid-dependent oxygenase. High-resolution structures for, apo-DAOCS, the enzyme complexed with Fe(II), and with Fe(II) and, 2-oxoglutarate, were obtained from merohedrally twinned crystals. Using a, model based on these structures, we propose a mechanism for ferryl, formation.

About this Structure

1DCS is a Single protein structure of sequence from Streptomyces clavuligerus with SO4 as ligand. Full crystallographic information is available from OCA.

Reference

Structure of a cephalosporin synthase., Valegard K, van Scheltinga AC, Lloyd MD, Hara T, Ramaswamy S, Perrakis A, Thompson A, Lee HJ, Baldwin JE, Schofield CJ, Hajdu J, Andersson I, Nature. 1998 Aug 20;394(6695):805-9. PMID:9723623

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