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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Carrier Proteins / chemistry
  • Catalytic Domain
  • Cations
  • Colistin / chemistry
  • Crystallography, X-Ray*
  • Escherichia coli Proteins / chemistry*
  • Ethanolamines / chemistry
  • Ions
  • Lipid A / chemistry
  • Membrane Proteins / chemistry
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Water / chemistry

Substances

  • Carrier Proteins
  • Cations
  • Escherichia coli Proteins
  • Ethanolamines
  • Ions
  • Lipid A
  • LptA protein, E coli
  • MCR-1 protein, E coli
  • Membrane Proteins
  • eptC protein, E coli
  • Water
  • phosphorylethanolamine
  • Colistin