Transition-State Vibrational Analysis and Isotope Effects for COMT-Catalyzed Methyl Transfer
![Thumbnail](/xmlui/bitstream/handle/10234/190067/Roca_2020.pdf.jpg?sequence=5&isAllowed=y)
Visualitza/
Metadades
Mostra el registre complet de l'elementcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/7013
comunitat-uji-handle3:10234/8638
comunitat-uji-handle4:
INVESTIGACIONMetadades
Títol
Transition-State Vibrational Analysis and Isotope Effects for COMT-Catalyzed Methyl TransferData de publicació
2020-08-19Editor
American Chemical SocietyCita bibliogràfica
ROCA, Maite; WILLIAMS, Ian H. Transition-State Vibrational Analysis and Isotope Effects for COMT-Catalyzed Methyl Transfer. Journal of the American Chemical Society, 2020, 142.36: 15548-15559.Tipus de document
info:eu-repo/semantics/articleVersió de l'editorial
https://pubs.acs.org/doi/10.1021/jacs.0c07344Versió
info:eu-repo/semantics/publishedVersionParaules clau / Matèries
Resum
Isotopic partition-function ratios (IPFRs) computed for transition structures (TSs) of the methyl-transfer reaction catalyzed by catechol O-methyltransferase and modeled by hybrid QM/MM methods are analyzed. The ability ... [+]
Isotopic partition-function ratios (IPFRs) computed for transition structures (TSs) of the methyl-transfer reaction catalyzed by catechol O-methyltransferase and modeled by hybrid QM/MM methods are analyzed. The ability of smaller Hessians to reproduce trends in α-3H3 and 14Cα IPFRs as obtained using the much larger subset QM/MM Hessians from which they are extracted is investigated critically. A 6-atom-extracted Hessian reproduces perfectly the α-T3 IPFR values from the full-subset Hessians of all the TSs but not the α-14CIPFRs. Average AM1/OPLS-AA harmonic frequencies and mean-square amplitudes are presented for the 12 normal modes of the α-CH3 moiety within the active site of several enzymic transition structures, together with QM/MM potential energy scans along each of these modes to assess the degree of anharmonicity. A novel investigation of ponderal effects upon IPFRs suggests that the value for α-14C tends toward a limiting minimum whereas that for α-T3 tends toward a limiting maximum as the mass of the rest of the system increases. The transition vector is dominated by motions of atoms within the donor and acceptor moieties and is very well described as a simple combination of Walden-inversion “umbrella” bending and asymmetric stretching of the SCα and CαO bonds. The contribution of atoms of the protein residues Met40, Tyr68, and Asp141 to the transition vector is extremely small. Average valence force constants for the COMT TS show significant differences from early BEBOVIB estimates which were used in support of the compression hypothesis for catalysis. There is no correlation between TS IPFRs and the nonbonded distances for close contacts between the S atom of SAM and Tyr68 or between any of the H atoms of the transferring methyl group and either Met40 or Asp141. [-]
Proyecto de investigación
Spanish Ministerio de Economía y Competitividad for a “Ramón y Cajal” contract (RYC-2014-16592) ; Spanish Ministerio de Ciencia, Innovación y Universidades (PGC2018-094852-B-C21) ; Generalitat Valenciana (AICO/2019/195) ; Universitat Jaume I (project UJI-B2019-43).Drets d'accés
© 2020 American Chemical Society
info:eu-repo/semantics/openAccess
info:eu-repo/semantics/openAccess
Apareix a les col.leccions
- QFA_Articles [819]
Els següents fitxers sobre la llicència estan associats a aquest element: