6b35: Difference between revisions
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==NMR ensemble of Tyrocidine A analogue AC3.28== | |||
<StructureSection load='6b35' size='340' side='right'caption='[[6b35]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6b35]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Brevibacillus_brevis Brevibacillus brevis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B35 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B35 FirstGlance]. <br> | |||
</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BE2:2-AMINOBENZOIC+ACID'>BE2</scene>, <scene name='pdbligand=DPN:D-PHENYLALANINE'>DPN</scene>, <scene name='pdbligand=ORN:L-ORNITHINE'>ORN</scene>, <scene name='pdbligand=PRD_002290:Tyrocidine+A+analogue+(DPN)(BE2)F(DPN)NKYV(ORN)L'>PRD_002290</scene></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=6b35 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b35 OCA], [https://pdbe.org/6b35 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b35 RCSB], [https://www.ebi.ac.uk/pdbsum/6b35 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b35 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The d-Phe-Pro beta-turn of the cyclic beta-hairpin antimicrobial decapeptide tyrocidine A, (Tyrc A) was substituted with the d-Phe-2-aminobenzoic acid (2-Abz) motif in a synthetic analogue (1). The NMR structure of 1 demonstrated that compound 1 retained the beta-hairpin structure of Tyrc A with additional planarity, resulting in approximately 30-fold reduced hemolysis than Tyrc A. Although antibacterial activity was partially compromised, a single Gln to Lys substitution (2) restored activity equivalent to Tyrc A against S. aureus, enhanced activity against two Gram negative strains and maintained the reduced hemeloysis of 1. Analysis by transmission electron microscopy (TEM) suggested a membrane lytic mechanism of action for these peptides. Compound 2 also exhibits nanomolar antifungal activity in synergy with amphotericin B. The d-Phe-2-Abz turn may serve as a tool for the synthesis of structurally predictable beta-hairpin libraries. Unlike traditional beta-turn motifs such as d-Pro-Gly, both the 2-Abz and d-Phe rings may be further functionalized. | |||
Tyrocidine A Analogues Bearing the Planar d-Phe-2-Abz Turn Motif: How Conformation Impacts Bioactivity.,Cameron AJ, Edwards PJB, Harjes E, Sarojini V J Med Chem. 2017 Nov 28. doi: 10.1021/acs.jmedchem.7b00953. PMID:29140694<ref>PMID:29140694</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6b35" style="background-color:#fffaf0;"></div> | ||
[[Category: Cameron | == References == | ||
[[Category: | <references/> | ||
[[Category: Harjes | __TOC__ | ||
</StructureSection> | |||
[[Category: Brevibacillus brevis]] | |||
[[Category: Large Structures]] | |||
[[Category: Cameron AJ]] | |||
[[Category: Ewdards PJB]] | |||
[[Category: Harjes E]] | |||
[[Category: Sarojini V]] | |||