Open AccessHigh resolution crystal structure of the catalytic domain of MCR-1
Author(s) -
Guixing Ma,
Yifan Zhu,
Zhicheng Yu,
Ashfaq Ahmad,
Hongmin Zhang
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep39540
Subject(s) - mcr 1 , crystal structure , chemistry , active site , transferase , stereochemistry , hydrolase , colistin , gene , catalysis , escherichia coli , biochemistry , enzyme , crystallography , enterobacteriaceae , antibiotics
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.