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- Title
Structure of the catalytic domain of the colistin resistance enzyme MCR-1.
- Authors
Stojanoski, Vlatko; Sankaran, Banumathi; Venkataram Prasad, B. V.; Poirel, Laurent; Nordmann, Patrice; Palzkill, Timothy
- 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.
- Subjects
COLISTIN; ENZYMES; MULTIDRUG resistance in bacteria; LIPOPOLYSACCHARIDES; BACTERIAL cell walls; THREONINE; PREVENTION
- Publication
BMC Biology, 2016, Vol 14, p1
- ISSN
1741-7007
- Publication type
Article
- DOI
10.1186/s12915-016-0303-0