6ct4

TFE-induced NMR structure of an antimicrobial peptide (EcDBS1R5) derived from a mercury transporter protein (MerP - Escherichia coli)

spinqualitylabelsall models 6ct4, 10 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ct4 is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 (<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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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