Stojanoski, Vlatko Sankaran, Banumathi Prasad, B. V. Venkataram Poirel, Laurent Nordmann, Patrice Palzkill, Timothy 2016-09-21 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. application/pdf https://folia.unifr.ch/global/documents/305155 https://folia.unifr.ch/documents/305155/files/nor_scd.pdf https://folia.unifr.ch/documents/305155/files/nor_scd_sm.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1186/s12915-016-0303-0 info:eu-repo/semantics/openAccess License undefined BMC Biology. - 2016, vol. 14, p. 81 info:eu-repo/classification/udc/57 Structure of the catalytic domain of the colistin resistance enzyme MCR-1 http://purl.org/coar/resource_type/c_6501