title: Role of Thiolate Ligand in Spin State and Redox Switching in the Cytochrome P450 Catalytic Cycle.
abstract: The catalytic cycle of cytochrome P450 involves a change from the resting-state, water-bound, six-coordinated form (1, low-spin state) to a five-coordinated form (2, high-spin state) upon binding of a hydrophobic substrate. Here, we used a heme-thiolate model complex (SR complex) with THF as a model of nonionic H2O to address the question of whether or not coordination of nonionic water is sufficient to induce the low-spin state. Measurements of electronic absorption spectra and magnetic properties confirmed that five-coordinated SR complex has a high-spin state, and THF-bound, six-coordinated SR has a low-spin state in dichloromethane at ambient temperature. The redox potential E1/2(FeII/FeIII) of THF-bound SR was 80-90 mV more negative than that of five-coordinated SR. These properties indicate SR is a good model of P450. Our results suggest that thiolate coordination plays a key role in setting the low energy barrier between the high-spin and low-spin states.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University , 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University , 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Inabe
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University , 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Shirakawa
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University , 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Umezawa
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University , 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Nobuki
authors.initials: N
authors.lastname: Kato
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University , 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Tsunehiko
authors.identifier: http://orcid.org/0000-0002-3586-4680
authors.initials: T
authors.lastname: Higuchi
mesh_terms: D055162:Biocatalysis; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008024:Ligands; D013438:Sulfhydryl Compounds; D003577:Cytochrome P-450 Enzyme System