Resistance to the “Last Resort” Antibiotic Colistin: A Single-Zinc Mechanism for Phosphointermediate Formation in MCR Enzymes

Emily Lythell; Reynier Suardíaz; Philip Hinchliffe; Chonnikan Hanpaibool; Surawit Visitsatthawong; A Sofia F Oliveira; Eric J M Lang; Panida Surawatanawong; Vannajan Sanghiran Lee; Thanyada Rungrotmongkol; Natalie Fey; James Spencer; Adrian J Mulholland

doi:10.1039/d0cc02520h

Resistance to the “Last Resort” Antibiotic Colistin: A Single-Zinc Mechanism for Phosphointermediate Formation in MCR Enzymes

Emily Lythell, Reynier Suardíaz, Philip Hinchliffe, Chonnikan Hanpaibool, Surawit Visitsatthawong, A Sofia F Oliveira, Eric J M Lang, Panida Surawatanawong, Vannajan Sanghiran Lee, Thanyada Rungrotmongkol, Natalie Fey, James Spencer, Adrian J Mulholland

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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.

Original language	English
Pages (from-to)	6874-6877
Number of pages	4
Journal	Chemical Communications
Volume	56
Issue number	50
Early online date	6 May 2020
DOIs	https://doi.org/10.1039/d0cc02520h
Publication status	Published - 25 Jun 2020

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This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Royal Society of Chemistry at https://pubs.rsc.org/en/content/articlelanding/2020/CC/D0CC02520H#!divAbstract. Please refer to any applicable terms of use of the publisher.
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This is the author accepted manuscript supplementary information (AAM). The final published version (version of record) is available online via Royal Society of Chemistry at https://pubs.rsc.org/en/content/articlelanding/2020/CC/D0CC02520H#!divAbstract. Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 1.88 MB

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Link account to CHEM RB1768 (EP/M027546/1) - Bristolbridge-Nanospears
Su, B. (Principal Investigator)
11/01/16 → 10/04/16
Project: Research
CCP-BioSim: Biomolecular Simulation at the Life Sciences Interface
Mulholland, A. J. (Principal Investigator)
1/07/15 → 30/04/21
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Lythell, E., Suardíaz, R., Hinchliffe, P., Hanpaibool, C., Visitsatthawong, S., Oliveira, A. S. F., Lang, E. J. M., Surawatanawong, P., Lee, V. S., Rungrotmongkol, T., Fey, N., Spencer, J., & Mulholland, A. J. (2020). Resistance to the “Last Resort” Antibiotic Colistin: A Single-Zinc Mechanism for Phosphointermediate Formation in MCR Enzymes. Chemical Communications, 56(50), 6874-6877 . https://doi.org/10.1039/d0cc02520h

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title = "Resistance to the “Last Resort” Antibiotic Colistin: A Single-Zinc Mechanism for Phosphointermediate Formation in MCR Enzymes",

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.",

author = "Emily Lythell and Reynier Suard{\'i}az and Philip Hinchliffe and Chonnikan Hanpaibool and Surawit Visitsatthawong and Oliveira, {A Sofia F} and Lang, {Eric J M} and Panida Surawatanawong and Lee, {Vannajan Sanghiran} and Thanyada Rungrotmongkol and Natalie Fey and James Spencer and Mulholland, {Adrian J}",

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doi = "10.1039/d0cc02520h",

language = "English",

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Lythell, E, Suardíaz, R , Hinchliffe, P, Hanpaibool, C, Visitsatthawong, S, Oliveira, ASF, Lang, EJM, Surawatanawong, P, Lee, VS, Rungrotmongkol, T, Fey, N , Spencer, J & Mulholland, AJ 2020, 'Resistance to the “Last Resort” Antibiotic Colistin: A Single-Zinc Mechanism for Phosphointermediate Formation in MCR Enzymes', Chemical Communications, vol. 56, no. 50, pp. 6874-6877 . https://doi.org/10.1039/d0cc02520h

TY - JOUR

T1 - Resistance to the “Last Resort” Antibiotic Colistin

T2 - A Single-Zinc Mechanism for Phosphointermediate Formation in MCR Enzymes

AU - Lythell, Emily

AU - Suardíaz, Reynier

AU - Hinchliffe, Philip

AU - Hanpaibool, Chonnikan

AU - Visitsatthawong, Surawit

AU - Oliveira, A Sofia F

AU - Lang, Eric J M

AU - Surawatanawong, Panida

AU - Lee, Vannajan Sanghiran

AU - Rungrotmongkol, Thanyada

AU - Fey, Natalie

AU - Spencer, James

AU - Mulholland, Adrian J

PY - 2020/6/25

Y1 - 2020/6/25

N2 - 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.

AB - 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.

U2 - 10.1039/d0cc02520h

DO - 10.1039/d0cc02520h

M3 - Article (Academic Journal)

C2 - 32432618

SN - 1359-7345

VL - 56

SP - 6874

EP - 6877

JO - Chemical Communications

JF - Chemical Communications

IS - 50

ER -

Resistance to the “Last Resort” Antibiotic Colistin: A Single-Zinc Mechanism for Phosphointermediate Formation in MCR Enzymes

Abstract

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Link account to CHEM RB1768 (EP/M027546/1) - Bristolbridge-Nanospears

CCP-BioSim: Biomolecular Simulation at the Life Sciences Interface

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HPC (High Performance Computing) and HTC (High Throughput Computing) Facilities

Cite this