1DRT

CRYSTAL STRUCTURE OF CLAVAMINATE SYNTHASE IN COMPLEX WITH FE(II), 2-OXOGLUTARATE AND PROCLAVAMINIC ACID

Summary for 1DRT

• Entry DOI: 10.2210/pdb1drt/pdb
• Related: 1DRY 1DS0 1DS1
• Descriptor: CLAVAMINATE SYNTHASE 1, 5-AMINO-3-HYDROXY-2-(2-OXO-AZETIDIN-1-YL)-PENTANOIC ACID, FE (II) ION, ... (5 entities in total)
• Functional Keywords: oxygenase, trifunctional enzyme, clavaminate synthase 1, oxidoreductase, lyase
• Biological source: Streptomyces clavuligerus
• Total number of polymer chains: 1
• Total formula weight: 35819.94

Authors

Zhang, Z.H.,Ren, J.,Stammers, D.K.,Baldwin, J.E.,Harlos, K.,Schofield, C.J. (deposition date: 2000-01-06, release date: 2000-07-06, Last modification date: 2024-02-07)

Primary citation

Zhang, Z.,Ren, J.,Stammers, D.K.,Baldwin, J.E.,Harlos, K.,Schofield, C.J.
Structural origins of the selectivity of the trifunctional oxygenase clavaminic acid synthase.
Nat.Struct.Biol., 7:127-133, 2000

PubMed Abstract: 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.

PubMed: 10655615
DOI: 10.1038/72398

Experimental method

X-RAY DIFFRACTION (2.1 Å)