title: Tyrosine oxidation in heme oxygenase: examination of long-range proton-coupled electron transfer.
abstract: Heme oxygenase is responsible for the degradation of a histidine-ligated ferric protoporphyrin IX (Por) to biliverdin, CO, and the free ferrous ion. Described here are studies of tyrosyl radical formation reactions that occur after oxidizing Fe(III)(Por) to Fe(IV)=O(Por(·+)) in human heme oxygenase isoform-1 (hHO-1) and the structurally homologous protein from Corynebacterium diphtheriae (cdHO). Site-directed mutagenesis on hHO-1 probes the reduction of Fe(IV)=O(Por(·+)) by tyrosine residues within 11 Å of the prosthetic group. In hHO-1, Y58· is implicated as the most likely site of oxidation, based on the pH and pD dependent kinetics. The absence of solvent deuterium isotope effects in basic solutions of hHO-1 and cdHO contrasts with the behavior of these proteins in the acidic solution, suggesting that long-range proton-coupled electron transfer predominates over electron transfer.
authors.affiliation: Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA, valeriy.smirnov@umontana.edu.
authors.forename: Valeriy V
authors.initials: VV
authors.lastname: Smirnov
authors.forename: Justine P
authors.initials: JP
authors.lastname: Roth
mesh_terms: D000595:Amino Acid Sequence; D003353:Corynebacterium diphtheriae / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D004579:Electron Transport; D006419:Heme Oxygenase (Decyclizing) / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010084:Oxidation-Reduction; D011522:Protons; D016415:Sequence Alignment; D014443:Tyrosine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D011522:Protons; D014443:Tyrosine; D006419:Heme Oxygenase (Decyclizing)