title: Electronic control of discrimination between O2 and CO in myoglobin lacking the distal histidine residue.
abstract: We analyzed the oxygen (O2) and carbon monoxide (CO) binding properties of the H64L mutant of myoglobin reconstituted with chemically modified heme cofactors possessing a heme Fe atom with a variety of electron densities, in order to elucidate the effect of the removal of the distal His64 on the control of both the O2 affinity and discrimination between O2 and CO of the protein by the intrinsic heme Fe reactivity through the electron density of the heme Fe atom (ρFe). The study revealed that, as in the case of the native protein, the O2 affinity of the H64L mutant protein is regulated by the ρFe value in such a manner that the O2 affinity of the protein decreases, due to an increase in the O2 dissociation rate constant, with a decrease in the ρFe value, and that the O2 affinities of the mutant and native proteins are affected comparably by a given change in the ρFe value. On the other hand, the CO affinity of the H64L mutant protein was found to increase, due to a decrease in the CO dissociation rate constant, with a decrease in the ρFe value, whereas that of the native protein was essentially independent of a change in the ρFe value. As a result, the regulation of the O2/CO discrimination in the protein through the ρFe value is affected by the distal His64. Thus, the study revealed that the electronic tuning of the intrinsic heme Fe reactivity through the ρFe value plays a vital role in the regulation of the protein function, as the heme environment furnished by the distal His64 does.
authors.affiliation: Department of Chemistry, University of Tsukuba , Tsukuba 305-8571, Japan.
authors.forename: Ryu
authors.initials: R
authors.lastname: Nishimura
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Shibata
authors.forename: Izumi
authors.initials: I
authors.lastname: Ishigami
authors.forename: Takashi
authors.initials: T
authors.lastname: Ogura
authors.forename: Hulin
authors.initials: H
authors.lastname: Tai
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nagao
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuo
authors.forename: Shun
authors.initials: S
authors.lastname: Hirota
authors.forename: Osami
authors.initials: O
authors.lastname: Shoji
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Imai
authors.forename: Saburo
authors.initials: S
authors.lastname: Neya
authors.forename: Akihiro
authors.initials: A
authors.lastname: Suzuki
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D004583:Electrons; D006418:Heme / Q000378:metabolism; D006639:Histidine; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009211:Myoglobin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D013379:Substrate Specificity; D014732:Vibration
chemical_list: D050505:Mutant Proteins; D009211:Myoglobin; D006418:Heme; D006639:Histidine; D002248:Carbon Monoxide; D010100:Oxygen