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|Title:||Cysteine deleted protegrin-1 (CDP-1) : anti-bacterial activity, outer-membrane disruption and selectivity||Authors:||Mohanram, Harini
|Keywords:||DRNTU::Science::Biological sciences::Biophysics||Issue Date:||2014||Source:||Mohanram, H., & Bhattacharjya, S. (2014). Cysteine deleted protegrin-1 (CDP-1) : anti-bacterial activity, outer-membrane disruption and selectivity. Biochimica et biophysica acta (BBA) - general subjects, 1840(10), 3006-3016.||Series/Report no.:||Biochimica et biophysica acta (BBA) - general subjects||Abstract:||BACKGROUND: Protegin-1 (PG-1: RGGRLCYCRRRFCVCVGR-amide) assumes a rigid β-hairpin like structure that is stabilized by two disulfide bridges between Cys6-Cys15 and Cys8-Cys13. Previous studies, employing linear analogs of PG-1, with Cys to Ala mutations or modified Cys, have demonstrated that the disulfide bridges are critical for the broad spectrum and salt resistant antimicrobial activity of PG-1. METHODS: In order to understand structural and functional roles of disulfide bonds in protegrins, we have synthesized a Cys deleted variant of PG-1 or CDP-1, RGGRLYRRRFVVGR-amide, and two of its analogs, RR11, RLYRRRFVVGR-amide, and LR10, LYRRRFVVGR-amide, containing deletion of residues at the N-terminus. These peptides have been characterized for bactericidal activity and mode of action in lipopolysaccharide (LPS) using optical spectroscopy, ITC and NMR. RESULTS: Antibacterial activity, against Gram-negative and Gram-positive strains, of the three peptides follows the order: CDP-1>RR11>LR10. LR10 displays only limited activity toward Gram-negative strains. CDP-1 demonstrates efficient membrane permeabilization and high-affinity interactions with LPS. CDP-1 and RR11 both assume β-hairpin like compact structures in complex with LPS, whereas LR10 adopts an extended conformation in LPS. In zwitterionic DPC micelles CDP-1 and the truncated analog peptides do not adopt folded conformations. MAJOR CONCLUSIONS: Despite the absence of stabilizing disulfide bridges CDP-1 shows broad-spectrum antibacterial activity and assumes β-hairpin like structure in complex with LPS. The β-hairpin structure may be essential for outer membrane permeabilization and cell killing.||URI:||https://hdl.handle.net/10356/97888
|ISSN:||0304-4165||DOI:||10.1016/j.bbagen.2014.06.018||Rights:||© 2014 Elsevier. This is the author created version of a work that has been peer reviewed and accepted for publication by Biochimica et Biophysica Acta (BBA) - General Subjects, Elsevier. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1016/j.bbagen.2014.06.018].||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Journal Articles|
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