Diatomic ligand discrimination by the heme oxygenases from Neisseria meningitidis and Pseudomonas aeruginosa

J Biol Chem. 2007 Jan 12;282(2):1066-71. doi: 10.1074/jbc.M609112200. Epub 2006 Nov 9.

Abstract

Heme oxygenases have an increased binding affinity for O2 relative to CO. Such discrimination is critical to the function of HO enzymes because one of the main products of heme catabolism is CO. Kinetic studies of mammalian and bacterial HO proteins reveal a significant decrease in the dissociation rate of O2 relative to other heme proteins such as myoglobin. Here we report the kinetic rate constants for the binding of O2 and CO by the heme oxygenases from Neisseria meningitidis (nmHO) and Pseudomonas aeruginosa (paHO). A combination of stopped-flow kinetic and laser flash photolysis experiments reveal that nmHO and paHO both maintain a similar degree of ligand discrimination as mammalian HO-1 and the HO from Corynebacterium diphtheriae. However, in addition to the observed decrease in dissociation rate for O2 by both nmHO and paHO, kinetic analyses show an increase in dissociation rate for CO by these two enzymes. The crystal structures of nmHO and paHO both contain significant differences from the mammalian HO-1 and bacterial C. diphtheriae HO structures, which suggests a structural basis for ligand discrimination in nmHO and paHO.

MeSH terms

  • Binding Sites
  • Carbon Dioxide / metabolism
  • Corynebacterium diphtheriae / enzymology
  • Crystallography
  • Electrochemistry
  • Heme / chemistry
  • Heme / metabolism
  • Heme Oxygenase (Decyclizing) / chemistry*
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Ligands
  • Membrane Proteins
  • Neisseria meningitidis / enzymology*
  • Neoplasm Proteins
  • Oxygen / metabolism
  • Pseudomonas aeruginosa / enzymology*
  • Substrate Specificity

Substances

  • FERMT1 protein, human
  • Ligands
  • Membrane Proteins
  • Neoplasm Proteins
  • Carbon Dioxide
  • Heme
  • Heme Oxygenase (Decyclizing)
  • Oxygen