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A kinetic model for the action of a resistance efflux pump

Walmsley, A.; Zhou, T.; Borges-Walmsley, M.I.; Rosen, B.P.

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


Authors

A. Walmsley

T. Zhou

M.I. Borges-Walmsley

B.P. Rosen



Contributors

M Borges-Walmsley vs000143@durham.ac.uk
Other

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.

Citation

Walmsley, A., Zhou, T., Borges-Walmsley, M., & Rosen, B. (2001). A kinetic model for the action of a resistance efflux pump. Journal of Biological Chemistry, 276(9), 6378-6391. https://doi.org/10.1074/jbc.m008105200

Journal Article Type Article
Publication Date Mar 2, 2001
Deposit Date Jan 9, 2008
Publicly Available Date Mar 29, 2024
Journal Journal of Biological Chemistry
Print ISSN 0021-9258
Electronic ISSN 1083-351X
Publisher American Society for Biochemistry and Molecular Biology
Peer Reviewed Peer Reviewed
Volume 276
Issue 9
Pages 6378-6391
DOI https://doi.org/10.1074/jbc.m008105200

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Copyright 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





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