XAS investigation of the structure and function of Ni in acireductone dioxygenase

Biochemistry. 2002 May 28;41(21):6761-9. doi: 10.1021/bi012209a.

Abstract

Acireductone dioxygenases (ARDs) are enzymes involved in the methionine recycle pathway, which regulates aspects of the cell cycle. Klebsiella pneumoniae produces two enzymes that share a common polypeptide sequence and differ only in the metal ion present. Reaction of acireductone (1,2-dihydroxy-3-keto-5-methylthiopentene) with Fe-ARD and dioxygen produces formate and 2-keto-4-methylthiobutanoic acid, the alpha-ketoacid precursor of methionine. Ni-ARD reacts with acireductone and dioxygen to produce methylthiopropionate, CO, and formate and does not lie on the methionine recycle pathway. An X-ray absorption spectroscopy (XAS) study of the structure of the catalytic Ni center in resting Ni-ARD enzyme and the enzyme-substrate complex is reported. This study establishes the structure of the Ni site in resting Ni-ARD as containing a six coordinate Ni site composed of O/N-donor ligands including 3-4 histidine residues, demonstrates that the substrate binds to the Ni center in a bidentate fashion by displacing two ligands, at least one of which is a histidine ligand, and provides insight into the mechanism of catalysis employed by a Ni-containing dioxygenase. Efficiently relaxed and hyperfine-shifted resonances are observed in the (1)H nuclear magnetic resonance spectrum of Ni-ARD that can be attributed to the His imidazoles ligating the paramagnetic Ni ion and are consistent with the XAS results regarding His ligation. These resonances show significant perturbation in the presence of substrate, confirming that the metal ion interacts directly with the substrate.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Catalytic Domain / physiology
  • Dioxygenases*
  • Histidine / chemistry*
  • Histidine / metabolism
  • Klebsiella pneumoniae / enzymology*
  • Nickel / chemistry*
  • Nickel / metabolism
  • Oxygenases / chemistry*
  • Oxygenases / metabolism
  • Spectrum Analysis / methods
  • Substrate Specificity
  • X-Rays

Substances

  • Histidine
  • Nickel
  • Oxygenases
  • Dioxygenases
  • aci-reductone oxidase (CO-forming)