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dc.contributor.authorMarkham, George D.
dc.contributor.authorTakusagawa, Fusao
dc.contributor.authorDiJuliio, Anthony M.
dc.contributor.authorBock, Charles W.
dc.date.accessioned2017-01-12T20:41:11Z
dc.date.available2017-01-12T20:41:11Z
dc.date.issued2010-12-01
dc.identifier.citationMarkham, George D., Fusao Takusagawa, Anthony M. Dijulio, and Charles W. Bock. "An Investigation of the Catalytic Mechanism of S-adenosylmethionine Synthetase by QM/MM Calculations." Archives of Biochemistry and Biophysics 492.1-2 (2009): 82-92.en_US
dc.identifier.urihttp://hdl.handle.net/1808/22632
dc.description.abstractCatalysis by S-adenosylmethionine synthetase has been investigated by quantum mechanical/molecular mechanical calculations, exploiting structures of the active crystalline enzyme. The transition state energy of +19.1 kcal/mol computed for a nucleophilic attack of the methionyl sulfur on carbon-5′ of the nucleotide was indistinguishable from the experimental (solution) value when the QM residues were an uncharged histidine that hydrogen bonds to the leaving oxygen-5′ and an aspartate that chelates a Mg2+ ion, and was similar (+18.8 kcal/mol) when the QM region also included the active site arginine and lysines. The computed energy difference between reactant and product was also consistent with their equimolar abundance in co-crystals. The calculated geometrical changes support catalysis of a SN2 reaction through hydrogen bonding of the liberated oxygen-5′ to the histidine, charge neutralization by the 2 Mg2+ ions, and stabilization of the product sulfonium cation through a close, non-bonded, contact between the sulfur and the ribose 4′-oxygen.en_US
dc.publisherElsevieren_US
dc.rightsThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subjectS-adenosylmethionineen_US
dc.subjectMethionine adenosyltransferaseen_US
dc.subjectEnzyme mechanismen_US
dc.subjectSubstrate-assisted-catalysisen_US
dc.subjectQM/MMen_US
dc.titleAn Investigation of the Catalytic Mechanism of S-adenosylmethionine Synthetase by QM/MM Calculationsen_US
dc.typeArticleen_US
kusw.kuauthorTakusagawa, Fusao
kusw.kudepartmentMolecular Biosciencesen_US
kusw.oanotesPer SHERPA/RoMEO 1/12/2017: Author's Pre-print: green tick author can archive pre-print (ie pre-refereeing) Author's Post-print: green tick author can archive post-print (ie final draft post-refereeing) Publisher's Version/PDF: cross author cannot archive publisher's version/PDF General Conditions: Authors pre-print on any website, including arXiv and RePEC Author's post-print on author's personal website immediately Author's post-print on open access repository after an embargo period of between 12 months and 48 months Permitted deposit due to Funding Body, Institutional and Governmental policy or mandate, may be required to comply with embargo periods of 12 months to 48 months Author's post-print may be used to update arXiv and RepEC Publisher's version/PDF cannot be used Must link to publisher version with DOI Author's post-print must be released with a Creative Commons Attribution Non-Commercial No Derivatives Licenseen_US
dc.identifier.doi10.1016/j.abb.2009.08.010en_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.rights.accessrightsopenAccess


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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Except where otherwise noted, this item's license is described as: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.