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Alternative substrates selective for S-adenosylmethionine synthetases from pathogenic bacteria
Stephen P Zano1, Pravin Bhansali, Amarjit Luniwal
1Department of Chemistry, The University of Toledo, Toledo, OH 43606, United States.
Archives of Biochemistry and Biophysics
|May 29, 2013
Summary
S-adenosyl-l-methionine (AdoMet) synthetase is crucial for bacterial metabolism and virulence. Researchers identified methionine analogs that can block bacterial quorum sensing while maintaining essential metabolic functions.
Area of Science:
- Biochemistry
- Microbiology
- Molecular Biology
Background:
- S-adenosyl-l-methionine (AdoMet) is a vital molecule in cellular metabolism, serving as the primary biological methyl donor.
- AdoMet also acts as a precursor for quorum sensing molecules that regulate virulence in Gram-negative bacteria.
Purpose of the Study:
- To investigate the S-adenosyl-l-methionine (AdoMet) synthetase enzyme from various pathogenic bacteria.
- To explore the potential of methionine analogs to inhibit bacterial virulence pathways.
Main Methods:
- Cloning, expression, and purification of AdoMet synthetase from pathogenic bacteria.
- Kinetic analysis of enzyme activity and substrate specificity using methionine analogs.
Main Results:
- AdoMet synthetase enzymes from Neisseria meningitidis and Escherichia coli exhibited similar kinetic parameters.
- The Pseudomonas aeruginosa enzyme showed reduced catalytic efficiency for MgATP.
- Campylobacter jejuni AdoMet synthetase displayed altered quaternary structure and higher catalytic turnover.
Conclusions:
- Methionine analogs can be potential inhibitors of bacterial quorum sensing.
- These analogs may offer a therapeutic strategy by disrupting virulence without compromising essential metabolic functions.
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