Brownian dynamic study of an enzyme metabolon in the TCA cycle: Substrate kinetics and channeling

Protein Science : a Publication of the Protein Society
Yu-Ming M HuangJ A McCammon

Abstract

Malate dehydrogenase (MDH) and citrate synthase (CS) are two pacemaking enzymes involved in the tricarboxylic acid (TCA) cycle. Oxaloacetate (OAA) molecules are the intermediate substrates that are transferred from the MDH to CS to carry out sequential catalysis. It is known that, to achieve a high flux of intermediate transport and reduce the probability of substrate leaking, a MDH-CS metabolon forms to enhance the OAA substrate channeling. In this study, we aim to understand the OAA channeling within possible MDH-CS metabolons that have different structural orientations in their complexes. Three MDH-CS metabolons from native bovine, wild-type porcine, and recombinant sources, published in recent work, were selected to calculate OAA transfer efficiency by Brownian dynamics (BD) simulations and to study, through electrostatic potential calculations, a possible role of charges that drive the substrate channeling. Our results show that an electrostatic channel is formed in the metabolons of native bovine and recombinant porcine enzymes, which guides the oppositely charged OAA molecules passing through the channel and enhances the transfer efficiency. However, the channeling probability in a suggested wild-type porcine metabolon c...Continue Reading

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Citations

Jan 24, 2018·Antimicrobial Agents and Chemotherapy·Lisandro J GonzálezAlejandro J Vila
Apr 27, 2019·Protein Science : a Publication of the Protein Society·Brian W Matthews
Jun 26, 2020·PLoS Computational Biology·Hadi RahmaninejadPeter Kekenes-Huskey
Jun 1, 2018·Nature Communications·Lee J Sweetlove, Alisdair R Fernie
Oct 4, 2020·Ecotoxicology and Environmental Safety·Jianzhao LiaoZhaoxin Tang
Jul 6, 2019·The Journal of Physical Chemistry. C, Nanomaterials and Interfaces·Yuanchao LiuScott Calabrese Barton
Sep 27, 2018·Biochemistry·Farzad MohajeraniAyusman Sen
Sep 22, 2021·Molecular Cell·Vidhi PareekStephen J Benkovic
Nov 10, 2020·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Joaquim Ferreira do Nascimento NetoWanderli Pedro Tadei

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