title: Can the local enzyme scaffold act as an H-donor for a Co(I)H bond formation? The curious case of methionine synthase-bound cob(I)alamin.
abstract: The density functional calculations and analysis of the existing X-ray crystallographic data have been carried out to gain mechanistic insight into the reactivation cycle of methionine synthase (MetH) enzyme. The calculations were carried out on the cobinamide-type model complexes of cob(I)alamin (Co(I)Cbx) testing H2O and PhOH as possible β-axial ligands. The PhOH motif was used to mimic the tyrosine (Y1139) residue that has been found in the active site of the MetH-bound cob(II)alamin (Co(II)Cbx). The calculations indicate that the β-axial PhOH ligand forms stronger Co(I)H bonds than H2O ligand due to its better H-donor capacity. The calculated redox tuning of Co(I)H interactions on the reduction potential of Co(II)/Co(I) couple (60-800 mV vs standard hydrogen electrode (SHE)), irrespective of the β-axial ligand considered, is significantly higher than the biological redox gap between the reduction potential of Co(II)/Co(I) couple and that of the biological reducing agents (50 mV vs SHE). The analysis of existing crystallographic data for the reactivation conformation of MetH enzyme (1K7Y (@3.0 Å); 1K98 (@3.8 Å) and 3IVA (@2.7 Å)) indicates that the Y1139 residue and the β-axial H2O ligand in the MetH-bound Co(II)Cbx complex are equidistant from the Co(II) ion (Y1139Co(II)=3.97 Å; H2OCo(II)=3.96 Å). Taking into account that the Y1139-induced Co(I)H linkages are thermodynamically more stable than the H2O-induced ones, the present calculations suggest that the Y1139 residue may serve as the β-axial ligand in the reactivation conformation of MetH enzyme.
authors.affiliation: 2320 South Brook Street, Department of Chemistry, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.forename: Pawel M
authors.initials: PM
authors.lastname: Kozlowski
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D055162:Biocatalysis; D020134:Catalytic Domain; D002414:Cations, Monovalent; D003035:Cobalt / Q000737:chemistry*; D003038:Cobamides / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004578:Electron Spin Resonance Spectroscopy; D004926:Escherichia coli / Q000737:chemistry* / Q000201:enzymology; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011522:Protons; D011789:Quantum Theory; D013816:Thermodynamics; D014443:Tyrosine / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D002414:Cations, Monovalent; D003038:Cobamides; D008024:Ligands; D011522:Protons; D014867:Water; C017142:cobinamide; D003035:Cobalt; D014443:Tyrosine; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
keywords: Co(I)H interaction; Co(II)/Co(I) reduction; Cob(I)alamin; Methionine synthase