Identification of peptide inhibitors of Pseudomonas aeruginosa exotoxin A function using a yeast two-hybrid approach
| Autor: | Dev Mangroo, A. Rod Merrill, Crista Thompson |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Virulence Factors
Bacterial Toxins Molecular Sequence Data Exotoxins Peptide Biology medicine.disease_cause Microbiology Peptide Library Two-Hybrid System Techniques Yeasts Genetics medicine Pseudomonas exotoxin Amino Acid Sequence Peptide library Molecular Biology chemistry.chemical_classification ADP Ribose Transferases Base Sequence Molecular biology Fusion protein Amino acid Enzyme Biochemistry chemistry Enzyme inhibitor Pseudomonas aeruginosa biology.protein Peptides Exotoxin |
| Zdroj: | FEMS microbiology letters. 218(1) |
| ISSN: | 0378-1097 |
| Popis: | The yeast two-hybrid system was used to identify peptide inhibitors of exotoxin A of Pseudomonas aeruginosa with the goal of using these to design peptide-based drugs against the toxin. A random peptide library consisting of 10(7) peptides ranging in length from 16 to 63 residues was screened for peptides that interact with the C-domain of exotoxin A. From the 10(7) transformants screened, three unique peptides of 63, 61 and 25 amino acids in length were found to specifically interact with the enzyme domain. The genes encoding these peptides were cloned and expressed as fusion proteins with the maltose-binding protein. In vitro inhibition measurements indicated that two of the peptides were modest inhibitors of toxin enzyme activity. These peptides now provide the basis for the development of more potent inhibitors, which will serve as lead inhibitors for evolution of potent peptide-based therapeutics. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text