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Published on: July 3, 2016
Structure and dynamics of the lantibiotic mutacin 1140
Leif Smith1, Cherian Zachariah, Ramanan Thirumoorthy
1University of Florida Interdisciplinary Graduate Program in Neuroscience, Gainesville, Florida 32611, USA.
Biochemistry
|September 3, 2003
Summary
Mutacin 1140, a lantibiotic from Streptococcus mutans, exhibits broad-spectrum antibacterial activity. Structural studies reveal it exists as an ensemble of flexible, horseshoe-shaped molecules, crucial for understanding its membrane interactions.
Area of Science:
- Microbiology
- Structural Biology
- Biochemistry
Background:
- Mutacin 1140 is a lantibiotic produced by Streptococcus mutans.
- Lantibiotics are ribosomally synthesized peptide bacteriocins characterized by lanthionine-containing structures.
- Mutacin 1140 demonstrates efficacy against various Gram-positive bacteria.
Purpose of the Study:
- To elucidate the three-dimensional structure of Mutacin 1140.
- To investigate the structural dynamics and flexibility of Mutacin 1140.
- To provide a structural basis for understanding Mutacin 1140's mechanism of action, including membrane interactions.
Main Methods:
- Chromatography and mass spectrometry were used to assess structural properties.
- Nuclear Magnetic Resonance (NMR) spectroscopy provided data on molecular structure.
- Restrained molecular dynamics simulations were employed to model structural ensembles.
- Scalar (J) coupling constant calculations were performed to validate structural models.
Main Results:
- Chromatography and mass spectrometry suggested a compact structure for Mutacin 1140.
- NMR data and molecular dynamics simulations indicated that Mutacin 1140 exists as an ensemble of interconverting structures.
- Calculations of scalar coupling constants supported the population-weighted ensemble model.
- Representative structures showed a common horseshoe-like shape with limited, well-defined flexible regions.
Conclusions:
- Mutacin 1140 adopts an ensemble of structures, not a single static conformation.
- The determined structures, particularly the horseshoe-like shape, are key to its function.
- These findings offer a foundation for modeling Mutacin 1140's interactions with bacterial membranes and pore formation.
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