6ct4

<StructureSection load='6ct4' size='340' side='right'caption='[[6ct4]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>

<table><tr><td colspan='2'>[[6ct4]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CT4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CT4 FirstGlance]. <br>

</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ct4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ct4 OCA], [http://pdbe.org/6ct4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ct4 RCSB], [http://www.ebi.ac.uk/pdbsum/6ct4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ct4 ProSAT]</span></td></tr>

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== Publication Abstract from PubMed ==

Computer-aided screening of antimicrobial peptides (AMPs) is a promising approach for discovering novel therapies against multidrug-resistant bacterial infections. Here, we functionally and structurally characterized an Escherichia coli-derived AMP (EcDBS1R5) previously designed through pattern identification [alpha-helical set (KK[ILV](3)[AILV])], followed by sequence optimization. EcDBS1R5 inhibited the growth of Gram-negative and Gram-positive, susceptible and resistant bacterial strains at low doses (2-32 muM), with no cytotoxicity observed against non-cancerous and cancerous cell lines in the concentration range analyzed (&lt;100 muM). Furthermore, EcDBS1R5 (16 muM) acted on Pseudomonas aeruginosa pre-formed biofilms by compromising the viability of biofilm-constituting cells. The in vivo antibacterial potential of EcDBS1R5 was confirmed as the peptide reduced bacterial counts by two-logs 2 days post-infection using a skin scarification mouse model. Structurally, circular dichroism analysis revealed that EcDBS1R5 is unstructured in hydrophilic environments, but has strong helicity in 2,2,2-trifluoroethanol (TFE)/water mixtures (v/v) and sodium dodecyl sulfate (SDS) micelles. The TFE-induced nuclear magnetic resonance structure of EcDBS1R5 was determined and showed an amphipathic helical segment with flexible termini. Moreover, we observed that the amide protons for residues Met2-Ala8, Arg10, Ala13-Ala16, and Trp19 in EcDBS1R5 are protected from the solvent, as their temperature coefficients values are more positive than -4.6 ppb.K(-1). In summary, this study reports a novel dual-antibacterial/antibiofilm alpha-helical peptide with therapeutic potential in vitro and in vivo against clinically relevant bacterial strains.

 

A Computationally Designed Peptide Derived from Escherichia coli as a Potential Drug Template for Antibacterial and Antibiofilm Therapies.,Cardoso MH, Candido ES, Chan LY, Der Torossian Torres M, Oshiro KGN, Rezende SB, Porto WF, Lu TK, de la Fuente-Nunez C, Craik DJ, Franco OL ACS Infect Dis. 2018 Dec 14;4(12):1727-1736. doi: 10.1021/acsinfecdis.8b00219., Epub 2018 Nov 1. PMID:30346140<ref>PMID:30346140</ref>

 

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 6ct4" style="background-color:#fffaf0;"></div>

[[Category: Candido, E S]]

[[Category: Cardoso, M H]]

[[Category: Chan, L Y]]

[[Category: Craik, D J]]

[[Category: Franco, O L]]

[[Category: Drug design]]