Stojanoski V Sankaran B Prasad BV Poirel L Nordmann P Palzkill T 2016 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. https://sonar.ch/global/documents/264410 eng info:eu-repo/semantics/altIdentifier/doi/10.1186/s12915-016-0303-0 info:eu-repo/semantics/altIdentifier/pmid/27655155 BMC biology. - 2016 Structure of the catalytic domain of the colistin resistance enzyme MCR-1. http://purl.org/coar/resource_type/c_6501