title: Intraprotein transmethylation via a CH3-Co(iii) species in myoglobin reconstituted with a cobalt corrinoid complex.
abstract: Myoglobin reconstituted with a cobalt tetradehydrocorrin derivative, rMb(Co(TDHC)), was investigated as a hybrid model to replicate the reaction catalyzed by methionine synthase. In the heme pocket, Co(I)(TDHC) is found to react with methyl iodide to form the methylated cobalt complex, CH3-Co(III)(TDHC), although it is known that a similar nucleophilic reaction of a cobalt(i) tetradehydrocorrin complex does not proceed effectively in organic solvents. Furthermore, we observed a residue- and regio-selective transmethylation from the CH3-Co(III)(TDHC) species to the Nε2 atom of the His64 imidazole ring in myoglobin at 25 °C over a period of 48 h. These findings indicate that the protein matrix promotes the model reaction of methionine synthase via the methylated cobalt complex. A theoretical calculation provides support for a plausible reaction mechanism wherein the axial histidine ligation stabilizes the methylated cobalt complex and subsequent histidine-flipping induces the transmethylation via heterolytic cleavage of the Co-CH3 bond in the hybrid model.
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita 565-0871, Japan. thayashi@chem.eng.osaka-u.ac.jp.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Morita
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita 565-0871, Japan. thayashi@chem.eng.osaka-u.ac.jp and Frontier Research Base for Global Young Researchers, Graduate School of Engineering, Osaka University, Suita 565-0871, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Oohora
authors.affiliation: Institute for Materials Chemistry and Engineering and International Research Centre for Molecular Systems, Kyushu University, Nishi-ku, Fukuoka 819-0395, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Sawada
authors.affiliation: Institute for Materials Chemistry and Engineering and International Research Centre for Molecular Systems, Kyushu University, Nishi-ku, Fukuoka 819-0395, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Doitomi
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita 565-0871, Japan. thayashi@chem.eng.osaka-u.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Ohbayashi
authors.affiliation: Institute for Materials Chemistry and Engineering and International Research Centre for Molecular Systems, Kyushu University, Nishi-ku, Fukuoka 819-0395, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kamachi
authors.affiliation: Institute for Materials Chemistry and Engineering and International Research Centre for Molecular Systems, Kyushu University, Nishi-ku, Fukuoka 819-0395, Japan and Elements Strategy Initiative for Catalysts and Batteries (ESICB), Kyoto University, Nishikyo-ku, Kyoto 615-8520, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yoshizawa
authors.affiliation: Department of Chemistry and Biochemistry, Graduate School of Engineering, Kyushu University, Fukuoka 819-0395, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hisaeda
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita 565-0871, Japan. thayashi@chem.eng.osaka-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hayashi
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D040761:Biomimetic Materials / Q000737:chemistry*; D003035:Cobalt / Q000737:chemistry*; D045728:Corrinoids / Q000737:chemistry*; D006418:Heme / Q000737:chemistry; D007700:Kinetics; D008745:Methylation; D008958:Models, Molecular; D009211:Myoglobin / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D045728:Corrinoids; D009211:Myoglobin; D009942:Organometallic Compounds; D003035:Cobalt; D006418:Heme; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase