Ab initio QM/MM study shows there is no general acid in the reaction catalyzed by 4-oxalocrotonate tautomerase

G. Andrés Cisneros, Haiyan Liu, Yingkai Zhang, Weitao Yang

Research output: Contribution to journalArticle

Abstract

The mechanism for the reaction catalyzed by the 4-oxalocrotonate tautomerase (4-OT) enzyme has been studied using a quantum mechanical/molecular mechanical (QM/MM) method developed in our laboratory. Total free energy barriers were obtained for the two steps involved in this reaction. In the first step, Pro-1 acts as a general base to abstract a proton from the third carbon of the substrate, 2-oxo-4-hexenedioate, creating a negative charge on the oxygen at C-2 of this substrate. In the second step, the same hydrogen abstracted by the N-terminal Pro-1 is shuttled back to the fifth carbon of the substrate to form the product, 2-oxo-3-hexenedioate. The calculated total free energy barriers are 14.54 and 16.45 kcal/mol for the first and second steps, respectively. Our calculations clearly show that there is no general acid in the reaction. Arg-39″, which is hydrogen bonded to the carboxylate group of the substrate, and an ordered water, which moves closer to the site of the charge formed in the transition state and intermediate, play the main role in transition state/intermediate stabilization without acting as general acids in the reaction.

Original languageEnglish (US)
Pages (from-to)10384-10393
Number of pages10
JournalJournal of the American Chemical Society
Volume125
Issue number34
DOIs
StatePublished - Aug 27 2003

Fingerprint

Hydrogen
Carbon
Acids
Energy barriers
Substrates
Free energy
Protons
Oxygen
Water
Enzymes
Stabilization
4-oxalocrotonate tautomerase

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Ab initio QM/MM study shows there is no general acid in the reaction catalyzed by 4-oxalocrotonate tautomerase. / Cisneros, G. Andrés; Liu, Haiyan; Zhang, Yingkai; Yang, Weitao.

In: Journal of the American Chemical Society, Vol. 125, No. 34, 27.08.2003, p. 10384-10393.

Research output: Contribution to journalArticle

@article{bb54acb115c54aeba82d4835b84cd9a4,
title = "Ab initio QM/MM study shows there is no general acid in the reaction catalyzed by 4-oxalocrotonate tautomerase",
abstract = "The mechanism for the reaction catalyzed by the 4-oxalocrotonate tautomerase (4-OT) enzyme has been studied using a quantum mechanical/molecular mechanical (QM/MM) method developed in our laboratory. Total free energy barriers were obtained for the two steps involved in this reaction. In the first step, Pro-1 acts as a general base to abstract a proton from the third carbon of the substrate, 2-oxo-4-hexenedioate, creating a negative charge on the oxygen at C-2 of this substrate. In the second step, the same hydrogen abstracted by the N-terminal Pro-1 is shuttled back to the fifth carbon of the substrate to form the product, 2-oxo-3-hexenedioate. The calculated total free energy barriers are 14.54 and 16.45 kcal/mol for the first and second steps, respectively. Our calculations clearly show that there is no general acid in the reaction. Arg-39″, which is hydrogen bonded to the carboxylate group of the substrate, and an ordered water, which moves closer to the site of the charge formed in the transition state and intermediate, play the main role in transition state/intermediate stabilization without acting as general acids in the reaction.",
author = "Cisneros, {G. Andr{\'e}s} and Haiyan Liu and Yingkai Zhang and Weitao Yang",
year = "2003",
month = "8",
day = "27",
doi = "10.1021/ja029672a",
language = "English (US)",
volume = "125",
pages = "10384--10393",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "34",

}

TY - JOUR

T1 - Ab initio QM/MM study shows there is no general acid in the reaction catalyzed by 4-oxalocrotonate tautomerase

AU - Cisneros, G. Andrés

AU - Liu, Haiyan

AU - Zhang, Yingkai

AU - Yang, Weitao

PY - 2003/8/27

Y1 - 2003/8/27

N2 - The mechanism for the reaction catalyzed by the 4-oxalocrotonate tautomerase (4-OT) enzyme has been studied using a quantum mechanical/molecular mechanical (QM/MM) method developed in our laboratory. Total free energy barriers were obtained for the two steps involved in this reaction. In the first step, Pro-1 acts as a general base to abstract a proton from the third carbon of the substrate, 2-oxo-4-hexenedioate, creating a negative charge on the oxygen at C-2 of this substrate. In the second step, the same hydrogen abstracted by the N-terminal Pro-1 is shuttled back to the fifth carbon of the substrate to form the product, 2-oxo-3-hexenedioate. The calculated total free energy barriers are 14.54 and 16.45 kcal/mol for the first and second steps, respectively. Our calculations clearly show that there is no general acid in the reaction. Arg-39″, which is hydrogen bonded to the carboxylate group of the substrate, and an ordered water, which moves closer to the site of the charge formed in the transition state and intermediate, play the main role in transition state/intermediate stabilization without acting as general acids in the reaction.

AB - The mechanism for the reaction catalyzed by the 4-oxalocrotonate tautomerase (4-OT) enzyme has been studied using a quantum mechanical/molecular mechanical (QM/MM) method developed in our laboratory. Total free energy barriers were obtained for the two steps involved in this reaction. In the first step, Pro-1 acts as a general base to abstract a proton from the third carbon of the substrate, 2-oxo-4-hexenedioate, creating a negative charge on the oxygen at C-2 of this substrate. In the second step, the same hydrogen abstracted by the N-terminal Pro-1 is shuttled back to the fifth carbon of the substrate to form the product, 2-oxo-3-hexenedioate. The calculated total free energy barriers are 14.54 and 16.45 kcal/mol for the first and second steps, respectively. Our calculations clearly show that there is no general acid in the reaction. Arg-39″, which is hydrogen bonded to the carboxylate group of the substrate, and an ordered water, which moves closer to the site of the charge formed in the transition state and intermediate, play the main role in transition state/intermediate stabilization without acting as general acids in the reaction.

UR - http://www.scopus.com/inward/record.url?scp=0042431983&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0042431983&partnerID=8YFLogxK

U2 - 10.1021/ja029672a

DO - 10.1021/ja029672a

M3 - Article

VL - 125

SP - 10384

EP - 10393

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 34

ER -