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Resistance to the “last resort” antibiotic colistin: a single-zinc mechanism for phosphointermediate formation in MCR enzymes

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Abstract

MCR (mobile colistin resistance) enzymes catalyse phosphoethanolamine (PEA) addition to bacterial lipid A, threatening the “last-resort” antibiotic colistin. Molecular dynamics and density functional theory simulations indicate that monozinc MCR supports PEA transfer to the Thr285 acceptor, positioning MCR as a mono- rather than multinuclear member of the alkaline phosphatase superfamily.

Graphical abstract: Resistance to the “last resort” antibiotic colistin: a single-zinc mechanism for phosphointermediate formation in MCR enzymes

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Article information


Submitted
08 Apr 2020
Accepted
06 May 2020
First published
06 May 2020

Chem. Commun., 2020, Advance Article
Article type
Communication

Resistance to the “last resort” antibiotic colistin: a single-zinc mechanism for phosphointermediate formation in MCR enzymes

E. Lythell, R. Suardíaz, P. Hinchliffe, C. Hanpaibool, S. Visitsatthawong, A. S. F. Oliveira, E. J. M. Lang, P. Surawatanawong, V. S. Lee, T. Rungrotmongkol, N. Fey, J. Spencer and A. J. Mulholland, Chem. Commun., 2020, Advance Article , DOI: 10.1039/D0CC02520H

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