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Sci Rep. 2016 Dec 21;6:39540. doi: 10.1038/srep39540.

High resolution crystal structure of the catalytic domain of MCR-1.

Author information

1
Department of Biology and Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, Shenzhen 518055, China.

Abstract

The newly identified mobile colistin resistant gene (mcr-1) rapidly spread among different bacterial strains and confers colistin resistance to its host, which has become a global concern. Based on sequence alignment, MCR-1 should be a phosphoethanolamine transferase, members of the YhjW/YjdB/YijP superfamily and catalyze the addition of phosphoethanolamine to lipid A, which needs to be validated experimentally. Here we report the first high-resolution crystal structure of the C-terminal catalytic domain of MCR-1 (MCR-1C) in its native state. The active pocket of native MCR-1C depicts unphosphorylated nucleophilic residue Thr285 in coordination with two Zinc ions and water molecules. A flexible adjacent active site loop (aa: Lys348-365) pose an open conformation compared to its structural homologues, suggesting of an open substrate entry channel. Taken together, this structure sets ground for further study of substrate binding and MCR-1 catalytic mechanism in development of potential therapeutic agents.

PMID:
28000749
PMCID:
PMC5175174
DOI:
10.1038/srep39540
[Indexed for MEDLINE]
Free PMC Article

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