The IsdG-family of haem oxygenases degrades haem to a novel chromophore.
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.
Reniere
Michelle L
ML
Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Ukpabi
Georgia N
GN
Harry
S Reese
SR
Stec
Donald F
DF
Krull
Robert
R
Wright
David W
DW
Bachmann
Brian O
BO
Murphy
Michael E
ME
Skaar
Eric P
EP
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*
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)