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Elucidating the GTP Hydrolysis Mechanism in FeoB – a Hydrophobic Amino Acid Substituted GTPase.

Neha, Vithani and Sahil, Batra and Balaji, Prakash and Nisanth, N. Nair (2017) Elucidating the GTP Hydrolysis Mechanism in FeoB – a Hydrophobic Amino Acid Substituted GTPase. ACS Catalysis, 7 (1). pp. 902-906.

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Abstract

Employing hybrid quantum mechanics/molecular dynamics (QM/MM) molecular dynamics simulations and experimental mutational studies, we investigate the GTP hydrolysis mechanism in a hydrophobic amino-acid substituted (HAS)-GTPase, FeoB. We identify glutamates, Glu66 and Glu67, that are acting as bases and find that proton transfer occurs from the attacking water to either of the glutamates through a water chain. However, GTP hydrolysis is not abolished, despite mutating these glutamates; instead, an alternative substrate-assisted hydrolysis becomes active with the same rate. Thus, mutational studies would misinterpret the role of glutamates. We trace the origin of the alternative mechanism to a structural feature conserved across all HAS-GTPases, distinct from the Ras-like GTPases.

Item Type: Article
Uncontrolled Keywords: Metadynamics, QM/MM, Metaphosphate, HAS-GTPase, Substrate-assisted-catalysis, Mutational studies, Proton transfer, Iron transporter
Subjects: 500 Natural Sciences and Mathematics > 07 Life Sciences > 03 Biochemistry & Molecular Biology > 07 Enzyme Biochemistry
Depositing User: Food Sci. & Technol. Information Services
Date Deposited: 22 Jan 2018 04:09
Last Modified: 22 Jan 2018 04:09
URI: http://ir.cftri.com/id/eprint/13347

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