Molecular basis for the substrate specificity of quorum signal synthases
| Autor: | Quin H. Christensen, Rajesh Nagarajan, Satish K. Nair, E. Peter Greenberg, Shi-Hui Dong, Nicole D. Frane |
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| Rok vydání: | 2017 |
| Předmět: |
Models
Molecular 0301 basic medicine S-Adenosylmethionine Protein Conformation Stereochemistry Homoserine Plasma protein binding Crystallography X-Ray Substrate Specificity Ligases 03 medical and health sciences chemistry.chemical_compound Protein structure Bacterial Proteins Biosynthesis Proteobacteria Amino Acid Sequence Peptide sequence chemistry.chemical_classification Multidisciplinary biology Quorum Sensing Biological Sciences Kinetics Acyl carrier protein Quorum sensing 030104 developmental biology Enzyme chemistry Biochemistry Mutation biology.protein lipids (amino acids peptides and proteins) Protein Binding Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 114:9092-9097 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | In several Proteobacteria, LuxI-type enzymes catalyze the biosynthesis of acyl–homoserine lactones (AHL) signals using S-adenosyl–l-methionine and either cellular acyl carrier protein (ACP)-coupled fatty acids or CoA–aryl/acyl moieties as progenitors. Little is known about the molecular mechanism of signal biosynthesis, the basis for substrate specificity, or the rationale for donor specificity for any LuxI member. Here, we present several cocrystal structures of BjaI, a CoA-dependent LuxI homolog that represent views of enzyme complexes that exist along the reaction coordinate of signal synthesis. Complementary biophysical, structure–function, and kinetic analysis define the features that facilitate the unusual acyl conjugation with S-adenosylmethionine (SAM). We also identify the determinant that establishes specificity for the acyl donor and identify residues that are critical for acyl/aryl specificity. These results highlight how a prevalent scaffold has evolved to catalyze quorum signal synthesis and provide a framework for the design of small-molecule antagonists of quorum signaling. |
| Databáze: | OpenAIRE |
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