1RXG

DEACETOXYCEPHALOSPORIN C SYNTHASE COMPLEXED WITH FE(II) AND 2-OXOGLUTARATE

Summary for 1RXG

• Entry DOI: 10.2210/pdb1rxg/pdb
• Descriptor: DEACETOXYCEPHALOSPORIN C SYNTHASE, FE (III) ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: ferrous oxygenase, cephalosporin, 2-oxoglutarate, antibiotics, merohedral twinning, oxidoreductase
• Biological source: Streptomyces clavuligerus
• Total number of polymer chains: 1
• Total formula weight: 34889.65

Authors

Valegard, K.,Terwisscha Van Scheltinga, A.C.,Lloyd, M.D.,Hara, T.,Ramaswamy, S.,Perrakis, A.,Thompson, A.,Lee, H.J.,Baldwin, J.E.,Shofield, C.J.,Hajdu, J.,Andersson, I. (deposition date: 1998-06-05, release date: 1999-06-08, Last modification date: 2024-02-14)

Primary citation

Valegard, K.,van Scheltinga, A.C.,Lloyd, M.D.,Hara, T.,Ramaswamy, S.,Perrakis, A.,Thompson, A.,Lee, H.J.,Baldwin, J.E.,Schofield, C.J.,Hajdu, J.,Andersson, I.
Structure of a cephalosporin synthase.
Nature, 394:805-809, 1998

PubMed Abstract: 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.

PubMed: 9723623
DOI: 10.1038/29575

Experimental method

X-RAY DIFFRACTION (1.5 Å)