1dcs
From Proteopedia
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'''DEACETOXYCEPHALOSPORIN C SYNTHASE FROM S. CLAVULIGERUS''' | '''DEACETOXYCEPHALOSPORIN C SYNTHASE FROM S. CLAVULIGERUS''' | ||
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[[Category: Valegard, K.]] | [[Category: Valegard, K.]] | ||
[[Category: 2-oxoglutarate]] | [[Category: 2-oxoglutarate]] | ||
- | [[Category: | + | [[Category: Antibiotic biosynthesis]] |
- | [[Category: | + | [[Category: Antibiotic]] |
- | [[Category: | + | [[Category: Cephalosporin]] |
- | [[Category: | + | [[Category: Ferrous oxygenase]] |
- | [[Category: | + | [[Category: Merohedral twinning]] |
- | [[Category: | + | [[Category: Oxidoreductase]] |
- | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:42:12 2008'' | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + |
Revision as of 10:42, 2 May 2008
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. 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 Page seeded by OCA on Fri May 2 13:42:12 2008
Categories: Single protein | Streptomyces clavuligerus | Andersson, I. | Baldwin, J E. | Hajdu, J. | Hara, T. | Lee, H J. | Lloyd, M D. | Perrakis, A. | Ramaswamy, S. | Scheltinga, A C.Terwisscha Van. | Schofield, C J. | Thompson, A. | Valegard, K. | 2-oxoglutarate | Antibiotic biosynthesis | Antibiotic | Cephalosporin | Ferrous oxygenase | Merohedral twinning | Oxidoreductase