Crystal structure of a clavaminate synthase-Fe(II)-2-oxoglutarate-substrate-NO complex: evidence for metal centered rearrangements

FEBS Lett. 2002 Apr 24;517(1-3):7-12. doi: 10.1016/s0014-5793(02)02520-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Crystallization
  • Crystallography, X-Ray
  • Iron / chemistry*
  • Iron / metabolism
  • Ketoglutaric Acids / chemistry*
  • Ketoglutaric Acids / metabolism
  • Mixed Function Oxygenases / chemistry*
  • Mixed Function Oxygenases / metabolism
  • Models, Molecular
  • Nitric Oxide / chemistry*
  • Nitric Oxide / metabolism
  • Protein Binding
  • Protein Conformation
  • Streptomyces / enzymology
  • Substrate Specificity
  • Water / chemistry

Substances

  • Ketoglutaric Acids
  • Water
  • Nitric Oxide
  • Iron
  • Mixed Function Oxygenases
  • clavaminate synthase