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Computer simulations of the reaction mechanisms in quinol:fumarate reductases

Grant number: 16/23525-0
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2017
Effective date (End): April 30, 2018
Field of knowledge:Biological Sciences - Biochemistry - Enzymology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Guilherme Menegon Arantes
Grantee:Felipe Curtolo
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Under normal conditions, aerobic organisms oxidize succinate to fumarate in the mitochondrial complex II, while anaerobic organisms, which use fumarate as the final electron acceptor of their catabolic pathways, catalyze the reverse reaction. Quinol:fumarate reductase (QFR) is the enzyme responsible for catalyzing the reaction in these anaerobic organisms. Even though aerobic organisms do not have genes that encode QFRs, they can also reduce fumarate under hypoxic conditions through complex II. However, the reaction catalytic efficiency in this direction is very low, indicating that the enzymatic mechanism of fumarate reduction may not be exactly the reverse of succinate oxidation. In this project, we propose to study the reaction mechanism of fumarate reduction in QFRs through computer simulations using hybrid quantum chemical/molecular mechanical (QC/MM) potentials. The results will help us understand in molecular level some open questions about the enzymatic reaction mechanism. Specifically, we will investigate the flavin electronic and charge state during reduction and the enzymatic regeneration mechanism. Also, we propose to determine the molecular basis that direct the oxireduction reaction of fumarate and succinate in collaboration with another project being developed in our research group with complex II. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CURTOLO, FELIPE; ARANTES, GUILHERME M.. Mechanisms for Flavin-Mediated Oxidation: Hydride or Hydrogen-Atom Transfer?. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. 60, n. 12, p. 6282-6287, . (16/23525-0, 16/24096-5, 17/26109-0, 19/21856-7)

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