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| | ==Cysteine Deleted Protegrin-1 (CDP-1): Anti-bacterial Activity, Outer-Membrane Disruption and Selectivity== | | ==Cysteine Deleted Protegrin-1 (CDP-1): Anti-bacterial Activity, Outer-Membrane Disruption and Selectivity== |
| - | <StructureSection load='2mq5' size='340' side='right'caption='[[2mq5]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2mq5' size='340' side='right'caption='[[2mq5]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mq5]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MQ5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2MQ5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mq5]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MQ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MQ5 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2mq2|2mq2]], [[2mq4|2mq4]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2mq5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mq5 OCA], [http://pdbe.org/2mq5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mq5 RCSB], [http://www.ebi.ac.uk/pdbsum/2mq5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2mq5 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2mq5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mq5 OCA], [https://pdbe.org/2mq5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mq5 RCSB], [https://www.ebi.ac.uk/pdbsum/2mq5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mq5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bhattacharjya, S]] | + | [[Category: Bhattacharjya S]] |
| - | [[Category: Mohanram, H]] | + | [[Category: Mohanram H]] |
| - | [[Category: Antimicrobial protein]]
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| - | [[Category: Random coil]]
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| Structural highlights
Publication Abstract from PubMed
BACKGROUND: Protegin-1 (PG-1: RGGRLCYCRRRFCVCVGR-amide) assumes a rigid beta-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 beta-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 beta-hairpin like structure in complex with LPS. The beta-hairpin structure may be essential for outer membrane permeabilization and cell killing.
Cysteine deleted protegrin-1 (CDP-1): Anti-bacterial activity, outer-membrane disruption and selectivity.,Mohanram H, Bhattacharjya S Biochim Biophys Acta. 2014 Jul 2. pii: S0304-4165(14)00238-4. doi:, 10.1016/j.bbagen.2014.06.018. PMID:24997421[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mohanram H, Bhattacharjya S. Cysteine deleted protegrin-1 (CDP-1): Anti-bacterial activity, outer-membrane disruption and selectivity. Biochim Biophys Acta. 2014 Jul 2. pii: S0304-4165(14)00238-4. doi:, 10.1016/j.bbagen.2014.06.018. PMID:24997421 doi:http://dx.doi.org/10.1016/j.bbagen.2014.06.018
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