Journal article
Structure of the catalytic domain of the colistin resistance enzyme MCR-1.
- Stojanoski V Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
- Sankaran B Berkeley Center for Structural Biology, Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley Laboratory, 1 Cyclotron Road, Berkeley, CA, 94720, USA.
- Prasad BV Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
- Poirel L Department of Medicine, Medical and Molecular Microbiology "Emerging Antibiotic Resistance" Unit and European INSERM Laboratory, IAME, University of Fribourg, Fribourg, Switzerland.
- Nordmann P Department of Medicine, Medical and Molecular Microbiology "Emerging Antibiotic Resistance" Unit and European INSERM Laboratory, IAME, University of Fribourg, Fribourg, Switzerland.
- Palzkill T Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, 77030, USA. timothyp@bcm.edu.
- 2016-09-23
Published in:
- BMC biology. - 2016
English
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.
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.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.1186/s12915-016-0303-0
- PMID 27655155
- Persistent URL
- https://sonar.ch/global/documents/264410
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