Crystal structure of a clavaminate synthase-Fe(II)-2-oxoglutarate-substrate-NO complex: evidence for metal centered rearrangements.
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.
Zhang
Zhihong
Z
The Oxford Centre for Molecular Sciences and The Dyson Perrins Laboratory, The Department of Chemistry, South Parks Road, Oxford, UK.
Ren
Jing shan
Js
Harlos
Karl
K
McKinnon
Colin H
CH
Clifton
Ian J
IJ
Schofield
Christopher J
CJ
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
D007656:Ketoglutaric Acids; D014867:Water; D009569:Nitric Oxide; D007501:Iron; D006899:Mixed Function Oxygenases; C066046:clavaminate synthase