Selection of peptide inhibitors against the Pseudomonas aeruginosa MurD cell wall enzyme
UNSPECIFIED. (2006) Selection of peptide inhibitors against the Pseudomonas aeruginosa MurD cell wall enzyme. PEPTIDES, 27 (7). pp. 1693-1700. ISSN 0196-9781Full text not available from this repository.
Official URL: http://dx.doi.org/10.1016/j.peptides.2006.01.017
The purified Pseudomonas aeruginosa cell wall biosynthesis MurD amide ligase enzyme was used to screen C-7-C and 12 mers peptides from phage display libraries using competitive biopanning approaches with the specific substrates D-glutamate and ATP. From the 60 phage-encoded peptides identified, DNA was sequenced, deduced amino acid sequences aligned and two peptides were synthesized from consensus sequences identified. The UDPN-acetylmuramyl-L-alanine MurD substrate was synthesized, purified and used to develop a spectrophotometric assay. One peptide synthesized was found to specifically inhibit ATPase activity of MurD. The IC50 value was estimated at 4 mu M for the C-7-C MurDp1 peptide. The loop conformation of MurDp1 was shown to be important for the inhibition of the UDP-N-acetylmuramyl-L-alanine:D-glutamate MurD ligase. The linear 12 mers MurD2 peptide has an IC50 value of 15 mM. A conserved amino acid motif was found between MurDp2 and the bacterial glyceraldehyde 3-phosphate dehydrogenase indicating that MurDp2 binds at a protein-protein interacting site. The approach proposed and results obtained suggest that efficient peptide inhibitors as well as protein-protein interaction domains can be identified by phage display. (c) 2006 Elsevier Inc. All rights reserved.
|Item Type:||Journal Article|
|Subjects:||Q Science > QD Chemistry
R Medicine > RS Pharmacy and materia medica
|Journal or Publication Title:||PEPTIDES|
|Publisher:||ELSEVIER SCIENCE INC|
|Number of Pages:||8|
|Page Range:||pp. 1693-1700|
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