title: The IsdG-family of haem oxygenases degrades haem to a novel chromophore.
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.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Reniere
authors.forename: Georgia N
authors.initials: GN
authors.lastname: Ukpabi
authors.forename: S Reese
authors.initials: SR
authors.lastname: Harry
authors.forename: Donald F
authors.initials: DF
authors.lastname: Stec
authors.forename: Robert
authors.initials: R
authors.lastname: Krull
authors.forename: David W
authors.initials: DW
authors.lastname: Wright
authors.forename: Brian O
authors.initials: BO
authors.lastname: Bachmann
authors.forename: Michael E
authors.initials: ME
authors.lastname: Murphy
authors.forename: Eric P
authors.initials: EP
authors.lastname: Skaar
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006418:Heme / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000737:chemistry / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013211:Staphylococcus aureus / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D006418:Heme; C497164:IsdI protein, Staphylococcus aureus; D006899:Mixed Function Oxygenases; D010105:Oxygenases; C482079:IsdG protein, Staphylococcus aureus; D006419:Heme Oxygenase (Decyclizing)