1ds1
From Proteopedia
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CRYSTAL STRUCTURE OF CLAVAMINATE SYNTHASE IN COMPLEX WITH FE(II) AND 2-OXOGLUTARATE
Overview
Clavaminate synthase (CAS), a remarkable Fe(II)/2-oxoglutarate oxygenase, catalyzes three separate oxidative reactions in the biosynthesis of clavulanic acid, a clinically used inhibitor of serine beta-lactamases. The first CAS-catalyzed step (hydroxylation) is separated from the latter two (oxidative cyclization/desaturation) by the action of an amidinohydrolase. Here, we describe crystal structures of CAS in complex with Fe(II), 2-oxoglutarate (2OG) and substrates (N-alpha-acetyl-L-arginine and proclavaminic acid). They reveal how CAS catalyzes formation of the clavam nucleus, via a process unprecedented in synthetic organic chemistry, and suggest how it discriminates between substrates and controls reaction of its highly reactive ferryl intermediate. The presence of an unpredicted jelly roll beta-barrel core in CAS implies divergent evolution within the family of 2OG and related oxygenases. Comparison with other non-heme oxidases/oxygenases reveals flexibility in the position which dioxygen ligates to the iron, in contrast to the analogous heme-using enzymes.
About this Structure
1DS1 is a Single protein structure of sequence from Streptomyces clavuligerus with , , and as ligands. Full crystallographic information is available from OCA.
Reference
Structural origins of the selectivity of the trifunctional oxygenase clavaminic acid synthase., Zhang Z, Ren J, Stammers DK, Baldwin JE, Harlos K, Schofield CJ, Nat Struct Biol. 2000 Feb;7(2):127-33. PMID:10655615
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