DFT/PM3 study of the enoyl-CoA hydratase catalyzed reaction

• Autorzy: Pawlak J. , Bahnson B. , Anderson V.
• Konferencja: Proceedings of the International Conference “2001 an Isotope Odyssey: New Application for a New Millenium", June 24-29, 2001, Zakopane, Poland
• Języki publikacji: EN

Abstrakty

EN

The enoyl-CoA hydratase catalyzed hydration of alfa,beta-unsaturated thiolesters has been modeled by using the crystal structure of 4-(N,N-dimethylamino)cinnamoyl-CoA bound at the active site. The quantum chemical calculation used the ONIOM mixed level procedure to permit the substrate thiolester and water molecule to be modeled using B3LYP/6-31G(d) level of theory and the active site residues modeled at a semiempirical level using the PM3 Hamiltonian. The results permitted the identification of a stable thiolester enolate intermediate, supporting a stepwise reaction mechanism. The calculation also suggests that the same proton removed from the nucleophilic water molecule is transferred to C alfa in the subsequent protonation of the enolate intermediate. This observation reconciles the stepwise mechanism with the previously reported double isotope effect study [3].

Słowa kluczowe

EN

coenzyme-A; density functional theory; enoyl-CoA hydratase; kinetic isotope effect; ONIOM model; stepwise mechanism; thiolester enolate

• Wydawca: Institute of Nuclear Chemistry and Technology
• Czasopismo: Nukleonika
• Rocznik: 2002
• Tom: Vol. 47,suppl.1
• Strony: 33--36
• Opis fizyczny: Bibliogr. 15 poz., rys.

Twórcy

autor

Pawlak J.

• Department of Biochemistry, Case Western Reserve University, 10900 Euclid Ave., Cleveland, Ohio 44106-4935, USA, Tel.: [phone], Fax: [phone]

autor

Bahnson B.

• Department of Biochemistry, Case Western Reserve University, 10900 Euclid Ave., Cleveland, Ohio 44106-4935, USA, Tel.: [phone], Fax: [phone]

autor

Anderson V.

• Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA

Bibliografia

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