An Investigation of the Catalytic Mechanism of S-adenosylmethionine Synthetase by QM/MM Calculations
dc.contributor.author | Markham, George D. | |
dc.contributor.author | Takusagawa, Fusao | |
dc.contributor.author | DiJuliio, Anthony M. | |
dc.contributor.author | Bock, Charles W. | |
dc.date.accessioned | 2017-01-12T20:41:11Z | |
dc.date.available | 2017-01-12T20:41:11Z | |
dc.date.issued | 2010-12-01 | |
dc.identifier.citation | Markham, 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.uri | http://hdl.handle.net/1808/22632 | |
dc.description.abstract | Catalysis 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.publisher | Elsevier | en_US |
dc.rights | 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. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | |
dc.subject | S-adenosylmethionine | en_US |
dc.subject | Methionine adenosyltransferase | en_US |
dc.subject | Enzyme mechanism | en_US |
dc.subject | Substrate-assisted-catalysis | en_US |
dc.subject | QM/MM | en_US |
dc.title | An Investigation of the Catalytic Mechanism of S-adenosylmethionine Synthetase by QM/MM Calculations | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Takusagawa, Fusao | |
kusw.kudepartment | Molecular Biosciences | en_US |
dc.identifier.doi | 10.1016/j.abb.2009.08.010 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.rights.accessrights | openAccess |
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