Selection of peptide inhibitors against the Pseudomonas aeruginosa MurD cell wall enzyme

Peptides
Catherine Paradis-BleauRoger C Levesque

Abstract

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 UDP-N-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 microM 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.

References

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Citations

Dec 23, 2008·BMC Biochemistry·Catherine Paradis-BleauRoger C Levesque
Nov 26, 2010·Critical Reviews in Biotechnology·Ankur GautamRupinder Tewari
Jun 28, 2011·European Journal of Medicinal Chemistry·Tihomir TomašićLucija Peterlin Mašič
Jul 28, 2010·Biotechnology Advances·Jyoti PandeAshok K Grover
May 29, 2008·Journal of Basic Microbiology·Tomaz BratkovicBorut Strukelj
Apr 30, 2009·The Biochemical Journal·Catherine Paradis-BleauRoger C Levesque
Feb 13, 2008·FEMS Microbiology Reviews·Hélène BarreteauDidier Blanot
Dec 2, 2014·Biomolecular Concepts·Roman ŠinkDidier Blanot

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