title: Structure of the catalytic domain of the colistin resistance enzyme MCR-1.
abstract: BACKGROUND
  Due to the paucity of novel antibiotics, colistin has become a last resort antibiotic for treating multidrug resistant bacteria. Colistin acts by binding the lipid A component of lipopolysaccharides and subsequently disrupting the bacterial membrane. The recently identified plasmid-encoded MCR-1 enzyme is the first transmissible colistin resistance determinant and is a cause for concern for the spread of this resistance trait. MCR-1 is a phosphoethanolamine transferase that catalyzes the addition of phosphoethanolamine to lipid A to decrease colistin affinity.
  
  
  RESULTS
  The structure of the catalytic domain of MCR-1 at 1.32 Å reveals the active site is similar to that of related phosphoethanolamine transferases.
  
  
  CONCLUSIONS
  The putative nucleophile for catalysis, threonine 285, is phosphorylated in cMCR-1 and a zinc is present at a conserved site in addition to three zincs more peripherally located in the active site. As noted for catalytic domains of other phosphoethanolamine transferases, binding sites for the lipid A and phosphatidylethanolamine substrates are not apparent in the cMCR-1 structure, suggesting that they are present in the membrane domain.
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.|Department of Pharmacology, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Vlatko
authors.initials: V
authors.lastname: Stojanoski
authors.affiliation: Berkeley Center for Structural Biology, Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley Laboratory, 1 Cyclotron Road, Berkeley, CA, 94720, USA.
authors.forename: Banumathi
authors.initials: B
authors.lastname: Sankaran
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: B V Venkataram
authors.initials: BV
authors.lastname: Prasad
authors.affiliation: Department of Medicine, Medical and Molecular Microbiology "Emerging Antibiotic Resistance" Unit and European INSERM Laboratory, IAME, University of Fribourg, Fribourg, Switzerland.
authors.forename: Laurent
authors.initials: L
authors.lastname: Poirel
authors.affiliation: Department of Medicine, Medical and Molecular Microbiology "Emerging Antibiotic Resistance" Unit and European INSERM Laboratory, IAME, University of Fribourg, Fribourg, Switzerland.|University of Lausanne, University Hospital Center, Lausanne, Switzerland.
authors.forename: Patrice
authors.initials: P
authors.lastname: Nordmann
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, 77030, USA. timothyp@bcm.edu.|Department of Pharmacology, Baylor College of Medicine, Houston, TX, 77030, USA. timothyp@bcm.edu.
authors.forename: Timothy
authors.identifier: http://orcid.org/0000-0002-5267-0001
authors.initials: T
authors.lastname: Palzkill