Reaction of cytochrome P450BM3 and peroxynitrite yields nitrosyl complex.
Peroxynitrite has come into the spotlight in recent years. Its effects on proteins have been implicated in several diseases such as acute lung injury, rheumatoid arthritis, implant rejection, artherosclerosis, Parkinson's disease, and Alzheimer's disease. Peroxynitrite is thought to inactivate a variety of proteins including thiolate-ligated heme proteins such as cytochrome P450 2B1 and PGI2 synthase, through the nitration of tyrosine residues. In previous studies it was reported that thiolate-ligated heme enzymes react with peroxynitrite to form a ferryl intermediate. In an effort to spectroscopically characterize this species in P450BM3, we discovered that the peroxynitrite-generated intermediate is not an FeIVoxo, but rather an iron-nitrosyl [FeNO]6 complex. We present density functional calculations as well as Mössbauer and stopped-flow spectroscopic characterizations of the peroxynitrite-generated intermediate in P450BM3.
Behan
Rachel K
RK
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Hoffart
Lee M
LM
Stone
Kari L
KL
Krebs
Carsten
C
Green
Michael T
MT
D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D008958:Models, Molecular; D009603:Nitroso Compounds / Q000737:chemistry*; D030421:Peroxynitrous Acid / Q000737:chemistry*; D013053:Spectrophotometry / Q000379:methods
D009603:Nitroso Compounds; D030421:Peroxynitrous Acid; D003577:Cytochrome P-450 Enzyme System