title: Crystal structure of a clavaminate synthase-Fe(II)-2-oxoglutarate-substrate-NO complex: evidence for metal centered rearrangements.
abstract: Clavaminate synthase (CAS), a 2-oxoglutarate (2OG) dependent dioxygenase, catalyses three steps in the biosynthesis of clavulanic acid. Crystals of CAS complexed with Fe(II), 2OG and deoxyguanidinoproclavaminate were exposed to nitric oxide (NO) acting as a dioxygen analogue. Prior to exposure with NO, the active site Fe(II) is octahedrally coordinated by a water molecule, the 2-oxo and 1-carboxylate groups of 2OG, and the side-chains of an aspartyl and two histidinyl residues. NO binds to the position previously occupied by the 2OG 1-carboxylate concomitant with rearrangement of the latter to the position previously occupied by the displaced water.
authors.affiliation: The Oxford Centre for Molecular Sciences and The Dyson Perrins Laboratory, The Department of Chemistry, South Parks Road, Oxford, UK.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jing shan
authors.initials: Js
authors.lastname: Ren
authors.forename: Karl
authors.initials: K
authors.lastname: Harlos
authors.forename: Colin H
authors.initials: CH
authors.lastname: McKinnon
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Clifton
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schofield
mesh_terms: D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D007501:Iron / Q000737:chemistry* / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000737:chemistry* / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D013302:Streptomyces / Q000201:enzymology; D013379:Substrate Specificity; D014867:Water / Q000737:chemistry
chemical_list: D007656:Ketoglutaric Acids; D014867:Water; D009569:Nitric Oxide; D007501:Iron; D006899:Mixed Function Oxygenases; C066046:clavaminate synthase