Structure of the catalytic domain of the colistin resistance enzyme MCR-1

Stojanoski, Vlatko; Sankaran, Banumathi; Prasad, B. V. Venkataram; Poirel, Laurent; Nordmann, Patrice; Palzkill, Timothy

doi:10.1186/s12915-016-0303-0

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Structure of the catalytic domain of the colistin resistance enzyme MCR-1

Stojanoski, Vlatko Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, USA - Department of Pharmacology, Baylor College of Medicine, Houston, USA
Sankaran, Banumathi Berkeley Center for Structural Biology, Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley Laboratory, Berkeley, USA
Prasad, B. V. Venkataram Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, USA
Poirel, Laurent Department of Medicine, Medical and Molecular Microbiology “Emerging Antibiotic Resistance” Unit and European INSERM Laboratory, IAME, University of Fribourg, Switzerland
Nordmann, Patrice Department of Medicine, Medical and Molecular Microbiology “Emerging Antibiotic Resistance” Unit and European INSERM Laboratory, IAME, University of Fribourg, Switzerland - University of Lausanne, University Hospital Center, Lausanne, Switzerland
Palzkill, Timothy Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, USA - Department of Pharmacology, Baylor College of Medicine, Houston, USA

21.09.2016

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BMC Biology. - 2016, vol. 14, p. 81

English 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.

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Faculté des sciences et de médecine

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Médecine 3ème année

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