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Matthews RG. Corrinoid- and cobalamin-dependent methyltransferases. In Metal-carbon bonds in enzymes and cofactors. Edited by Sigal A, Sigal H, Sigal RKO: Royal Society of Chemistry; 2009 [Metal Ions in Life Sciences, vol 6.], in press.
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The genome of M. acetivorans reveals extensive metabolic and physiological diversity
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Cobalamin-dependent methionine synthase is a modular protein with distinct regions for binding homocysteine, methyltetrahydrofolate, cobalamin, and adenosylmethionine
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Goulding C.W., Postigo D., and Matthews R.G. Cobalamin-dependent methionine synthase is a modular protein with distinct regions for binding homocysteine, methyltetrahydrofolate, cobalamin, and adenosylmethionine. Biochemistry 36 (1997) 8082-8091
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Goulding, C.W.1
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Structures of the N-terminal modules imply large domain motions during catalysis by methionine synthase
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Evans J.C., Huddler D.P., Hilgers M.T., Romanchuk G., Matthews R.G., and Ludwig M.L. Structures of the N-terminal modules imply large domain motions during catalysis by methionine synthase. Proc Natl Acad Sci U S A 101 (2004) 3729-3736
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Assignment of enzymic function to specific protein regions of cobalamin-dependent methionine synthase from Escherichia coli
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Drummond J.T., Huang S., Blumenthal R.M., and Matthews R.G. Assignment of enzymic function to specific protein regions of cobalamin-dependent methionine synthase from Escherichia coli. Biochemistry 32 (1993) 9290-9295
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Biochemistry
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Drummond, J.T.1
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Crystal structure and solution characterization of the activation domain of human methionine synthase
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Wolthers K.R., Toogood H.S., Jowitt T.A., Marshall K.R., Leys D., and Scrutton N.S. Crystal structure and solution characterization of the activation domain of human methionine synthase. FEBS J 274 (2007) 738-750
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A disulfide-stabilized conformer of methionine synthase reveals an unexpected role for the histidine ligand of the cobalamin cofactor
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A disulfide cross-link was engineered to stabilize the AdoMet:Cob conformation and enable the crystallization of the C-terminal half of methionine synthase. The structure provides the first view of His759 in the His-off AdoMet:Cob conformation. In this conformation, His759 is involved in intermodular hydrogen bonding interactions with the AdoMet-binding domain that are proposed to play a role in stabilization of the activation conformation.
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Datta S., Koutmos M., Pattridge K.A., Ludwig M.L., and Matthews R.G. A disulfide-stabilized conformer of methionine synthase reveals an unexpected role for the histidine ligand of the cobalamin cofactor. Proc Natl Acad Sci U S A. 105 (2008) 4115-4120. A disulfide cross-link was engineered to stabilize the AdoMet:Cob conformation and enable the crystallization of the C-terminal half of methionine synthase. The structure provides the first view of His759 in the His-off AdoMet:Cob conformation. In this conformation, His759 is involved in intermodular hydrogen bonding interactions with the AdoMet-binding domain that are proposed to play a role in stabilization of the activation conformation.
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Methionine synthase exists in two distinct conformations that differ in reactivity toward methyltetrahydrofolate, adenosylmethionine, and flavodoxin
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Jarrett J.T., Huang S., and Matthews R.G. Methionine synthase exists in two distinct conformations that differ in reactivity toward methyltetrahydrofolate, adenosylmethionine, and flavodoxin. Biochemistry 37 (1998) 5372-5382
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Jarrett, J.T.1
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Goulding C.W., and Matthews R.G. Cobalamin-dependent methionine synthase from Escherichia coli: involvement of zinc in homocysteine activation. Biochemistry 36 (1997) 15749-15757
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Metal active site elasticity linked to activation of homocysteine in methionine synthases
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The zinc atom in MetH is shown to be ligated by three cysteines and a asparagyl residue in the resting enzyme and to expel the asparagyl ligand with an inversion in its geometry as homocysteine is bound. Associated with inversion, the zinc moves more than 2 Å upon homocysteine binding. This unexpected flexiblity in the metal center is proposed to facilitate methyltransfer and product release.
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Koutmos M., Pejchal R., Bomer T.M., Matthews R.G., Smith J.L., and Ludwig M.L. Metal active site elasticity linked to activation of homocysteine in methionine synthases. Proc Natl Acad Sci U S A 105 (2008) 3286-3291. The zinc atom in MetH is shown to be ligated by three cysteines and a asparagyl residue in the resting enzyme and to expel the asparagyl ligand with an inversion in its geometry as homocysteine is bound. Associated with inversion, the zinc moves more than 2 Å upon homocysteine binding. This unexpected flexiblity in the metal center is proposed to facilitate methyltransfer and product release.
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Proc Natl Acad Sci U S A
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Koutmos, M.1
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Mossbauer, EPR, and optical studies of the corrinoid/iron-sulfur protein involved in the synthesis of acetyl coenzyme A by Clostridium thermoaceticum
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Ragsdale S.W., Lindahl P.A., and Munck E. Mossbauer, EPR, and optical studies of the corrinoid/iron-sulfur protein involved in the synthesis of acetyl coenzyme A by Clostridium thermoaceticum. J Biol Chem 262 (1987) 14289-14297
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Spectroscopic studies of the corrinoid/iron-sulfur protein from Moorella thermoacetica
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Elegant spectroscopic/computational studies show that in the cobalt(III) and cobalt(II) states the enzyme-bound corrinoid is base-off with water as the axial ligand.
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Stich T.A., Seravalli J., Venkateshrao S., Spiro T.G., Ragsdale S.W., and Brunold T.C. Spectroscopic studies of the corrinoid/iron-sulfur protein from Moorella thermoacetica. J Am Chem Soc 128 (2006) 5010-5020. Elegant spectroscopic/computational studies show that in the cobalt(III) and cobalt(II) states the enzyme-bound corrinoid is base-off with water as the axial ligand.
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Stich, T.A.1
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Structural insights into methyltransfer reactions of a corrinoid iron-sulfur protein involved in acetyl-CoA synthesis
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The crystal structure reveals the relative position of the smaller subunit above the bound base-off cobalamin moiety with a water molecule occupying the β-axial position.
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Svetlitchnaia T., Svetlitchnyi V., Meyer O., and Dobbek H. Structural insights into methyltransfer reactions of a corrinoid iron-sulfur protein involved in acetyl-CoA synthesis. Proc Natl Acad Sci U S A 103 (2006) 14331-14336. The crystal structure reveals the relative position of the smaller subunit above the bound base-off cobalamin moiety with a water molecule occupying the β-axial position.
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Doukov T., Seravelli J., Stezowski J.J., and Ragsdale S.W. Crystal structure of a methyltetrahydrofolate- and corrinoid-dependent methyltransferase. Structure 8 (2000) 817-830
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This paper reveals the network required for protonation of methyltetrahydrofolate in the corrinoid iron-sulfur protein methyltransferase AcsE. The hydrogen bonding of the enzyme-methyltetrahydrofolate complex is shown. Asn199 is proposed serve as a hydrogen bond acceptor to N5 of protonated methyltetrahydrofolate, by analogy with the role of Asn in purine nucleotide phosphorylase. Mutation of Asn199 is shown to decrease the activity by ∼20 000-fold, but to have only a minor effect on the binding of methyltetrahydrofolate.
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Doukov T.I., Hemmi H., Drennan C.L., and Ragsdale S.W. Structural and kinetic evidence for an extended hydrogen-bonding network in catalysis of methyl group transfer: role of an active site asparagine residue in activation of methyl transfer by methyltransferases. Biochemistry 282 (2007) 6609-6618. This paper reveals the network required for protonation of methyltetrahydrofolate in the corrinoid iron-sulfur protein methyltransferase AcsE. The hydrogen bonding of the enzyme-methyltetrahydrofolate complex is shown. Asn199 is proposed serve as a hydrogen bond acceptor to N5 of protonated methyltetrahydrofolate, by analogy with the role of Asn in purine nucleotide phosphorylase. Mutation of Asn199 is shown to decrease the activity by ∼20 000-fold, but to have only a minor effect on the binding of methyltetrahydrofolate.
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Sauer K., and Thauer R.K. Methanol:coenzyme M methyltransferase from Methanosarcina barkeri: zinc dependence and thermodynamics of the methanol:cob(I)alamin methyltransferase reaction. Eur J Biochem 249 (1997) 280-285
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Sauer K., and Thauer R.K. Methyl-coenzyme M formation in methanogenic archaea. Involvement of zinc in coenzyme M activation. Eur J Biochem 267 (2000) 2498-2504
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Sauer K., and Thauer T.K. Methanol:coenzyme M methyltransferase from Methanosarcina barkeri: identification of the active-site histidine in the corrinoid-harboring subunit MtaC by site-directed mutagenesis. Eur J Biochem 253 (1998) 698-705
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Das A., Fu Z.-Q., Tempel W., Liu Z.-J., Chang J., Chen L., Lee D., Zhou W., Xu H., Shaw N., et al. Characterization of a corrinoid protein involved in the C1 metabolism of strict anaerobic bacterium Moorella thermoacetica. Proteins 67 (2007) 167-176
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Insight into the mechanism of biological methanol activation based on the crystal structure of the methanol-cobalamin methyltransferase complex
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In this paper, the structure for the cobalamin-containing MtaC protein docked with its partner MtaB, which contains a binding site for coenzyme M has been determined. This is thus far the only structure available for a corrinoid-dependent methyltransferase docked with a substrate-binding domain.
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Hagemeier C.H., Kruer M., Thauer R.K., Warkentin E., and Ermler U. Insight into the mechanism of biological methanol activation based on the crystal structure of the methanol-cobalamin methyltransferase complex. Proc Natl Acad Sci U S A 103 (2006) 18917-18922. In this paper, the structure for the cobalamin-containing MtaC protein docked with its partner MtaB, which contains a binding site for coenzyme M has been determined. This is thus far the only structure available for a corrinoid-dependent methyltransferase docked with a substrate-binding domain.
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Access to the AdoMet:Cob conformation of methionine synthase is governed by the trans effect conveyed by the upper axial ligand to the cobalt of cobalamin, as well as by the net charge on the cobalt. Increasing electron density on the cobalt, whether induced by the trans axial ligand or by reduction of the cobalt, favors entrance into the AdoMet:Cob conformation.
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Fleischhacker A.S., and Matthews R.G. Ligand trans influence governs conformation in cobalamin-dependent methionine synthase. Biochemistry 46 (2007) 12382-12392. Access to the AdoMet:Cob conformation of methionine synthase is governed by the trans effect conveyed by the upper axial ligand to the cobalt of cobalamin, as well as by the net charge on the cobalt. Increasing electron density on the cobalt, whether induced by the trans axial ligand or by reduction of the cobalt, favors entrance into the AdoMet:Cob conformation.
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