title: High resolution crystal structure of the catalytic domain of MCR-1.
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.
authors.affiliation: Department of Biology and Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, Shenzhen 518055, China.
authors.forename: Guixing
authors.initials: G
authors.lastname: Ma
authors.affiliation: Department of Biology and Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, Shenzhen 518055, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Biology and Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, Shenzhen 518055, China.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Biology and Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, Shenzhen 518055, China.
authors.forename: Ashfaq
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Biology and Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, Shenzhen 518055, China.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Zhang
mesh_terms: D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry; D020134:Catalytic Domain; D002412:Cations; D003091:Colistin / Q000737:chemistry; D018360:Crystallography, X-Ray; D029968:Escherichia coli Proteins / Q000737:chemistry*; D004983:Ethanolamines / Q000737:chemistry; D007477:Ions; D008050:Lipid A / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D014867:Water / Q000737:chemistry
chemical_list: D002352:Carrier Proteins; D002412:Cations; D029968:Escherichia coli Proteins; D004983:Ethanolamines; D007477:Ions; D008050:Lipid A; C532155:LptA protein, E coli; C000614037:MCR-1 protein, E coli; D008565:Membrane Proteins; C121439:eptC protein, E coli; D014867:Water; C005448:phosphorylethanolamine; D003091:Colistin