The IsdG-family of haem oxygenases degrades haem to a novel chromophore

Mol Microbiol. 2010 Mar;75(6):1529-38. doi: 10.1111/j.1365-2958.2010.07076.x. Epub 2010 Feb 17.

Abstract

Enzymatic haem catabolism by haem oxygenases is conserved from bacteria to humans and proceeds through a common mechanism leading to the formation of iron, carbon monoxide and biliverdin. The first members of a novel class of haem oxygenases were recently identified in Staphylococcus aureus (IsdG and IsdI) and were termed the IsdG-family of haem oxygenases. Enzymes of the IsdG-family form tertiary structures distinct from those of the canonical haem oxygenase family, suggesting that IsdG-family members degrade haem via a unique reaction mechanism. Herein we report that the IsdG-family of haem oxygenases degrade haem to the oxo-bilirubin chromophore staphylobilin. We also present the crystal structure of haem-bound IsdI in which haem ruffling and constrained binding of oxygen is consistent with cleavage of the porphyrin ring at the beta- or delta-meso carbons. Combined, these data establish that the IsdG-family of haem oxygenases degrades haem to a novel chromophore distinct from biliverdin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism*
  • Crystallography, X-Ray
  • Heme / metabolism*
  • Heme Oxygenase (Decyclizing) / chemistry
  • Heme Oxygenase (Decyclizing) / metabolism
  • Mixed Function Oxygenases / chemistry*
  • Mixed Function Oxygenases / metabolism*
  • Models, Molecular
  • Molecular Structure
  • Oxidation-Reduction
  • Oxygenases / chemistry*
  • Oxygenases / metabolism*
  • Protein Structure, Tertiary
  • Staphylococcus aureus / enzymology*

Substances

  • Bacterial Proteins
  • Heme
  • IsdI protein, Staphylococcus aureus
  • Mixed Function Oxygenases
  • Oxygenases
  • IsdG protein, Staphylococcus aureus
  • Heme Oxygenase (Decyclizing)

Associated data

  • PDB/3LGM
  • PDB/3LGN