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A kinetic model for the action of a resistance efflux pump.

Walmsley, A. and Zhou, T. and Borges-Walmsley, M. I. and Rosen, B. P. (2001) 'A kinetic model for the action of a resistance efflux pump.', Journal of biological chemistry., 276 (9). pp. 6378-6391.

Abstract

ArsA is the catalytic subunit of the arsenical pump, coupling ATP hydrolysis to the efflux of arsenicals through the ArsB membrane protein. It is a paradigm for understanding the structure-function of the nucleotide binding domains (NBD) of medically important efflux pumps, such as P-glycoprotein, because it has two sequence-related, interacting NBD, for which the structure is known. On the basis of a rigorous analysis of the pre-steady-state kinetics of nucleotide binding and hydrolysis, we propose a model in which ArsA alternates between two mutually exclusive conformations as follows: the ArsA1 conformation in which the A1 site is closed but the A2 site open; and the ArsA2 conformation, in which the A1 and A2 sites are open and closed, respectively. Antimonite elicits its effects by sequestering ArsA in the ArsA1 conformation, which catalyzes rapid ATP hydrolysis at the A2 site to drive ArsA between conformations that have high (nucleotide-bound ArsA) and low affinity (nucleotide-free ArsA) for Sb(III). ArsA potentially utilizes this process to sequester Sb(III) from the medium and eject it into the channel of ArsB.

Item Type:Article
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Status:Peer-reviewed
Publisher Web site:https://doi.org/10.1074/jbc.M008105200
Publisher statement:This research was originally published in Journal of Biological Chemistry. Adrian R. Walmsley, Tongqing Zhou, M. Ines Borges-Walmsley, Barry P. Rosen. Title. Journal of Biological Chemistry. 2000. 276: 6378-6391. © the American Society for Biochemistry and Molecular Biology
Record Created:09 Jan 2008
Last Modified:30 Aug 2017 09:38

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