8gak
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of E. coli LptA in complex with Chinavia Ubica Thanatin== | |
| + | <StructureSection load='8gak' size='340' side='right'caption='[[8gak]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8gak]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Chinavia_ubica Chinavia ubica] and [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GAK FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</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=8gak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gak OCA], [https://pdbe.org/8gak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gak RCSB], [https://www.ebi.ac.uk/pdbsum/8gak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gak ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/A0A6D0DFJ5_ECOLX A0A6D0DFJ5_ECOLX] Involved in the assembly of lipopolysaccharide (LPS). Required for the translocation of LPS from the inner membrane to the outer membrane. May form a bridge between the inner membrane and the outer membrane, via interactions with LptC and LptD, thereby facilitating LPS transfer across the periplasm.[HAMAP-Rule:MF_01914] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Podisus maculiventris thanatin has been reported as a potent antimicrobial peptide with antibacterial and antifungal activity. Its antibiotic activity has been most thoroughly characterized against E. coli and shown to interfere with multiple pathways, such as the lipopolysaccharide transport (LPT) pathway comprised of seven different Lpt proteins. Thanatin binds to E. coli LptA and LptD, thus disrupting the LPT complex formation and inhibiting cell wall synthesis and microbial growth. Here, we performed a genomic database search to uncover novel thanatin orthologs, characterized their binding to E. coli LptA using bio-layer interferometry, and assessed their antimicrobial activity against E. coli. We found that thanatins from Chinavia ubica and Murgantia histrionica bound tighter (by 3.6- and 2.2-fold respectively) to LptA and exhibited more potent antibiotic activity (by 2.1- and 2.8-fold respectively) than the canonical thanatin from P. maculiventris. We crystallized and determined the LptA-bound complex structures of thanatins from C. ubica (1.90 A resolution), M. histrionica (1.80 A resolution), and P. maculiventris (2.43 A resolution) to better understand their mechanism of action. Our structural analysis revealed that residues A10 and I21 in C. ubica and M. histrionica thanatin are important for improving the binding interface with LptA, thus overall improving the potency of thanatin against E. coli. We also designed a stapled variant of thanatin that removes the need for a disulfide bond but retains the ability to bind LptA and antibiotic activity. Our discovery presents a library of novel thanatin sequences to serve as starting scaffolds for designing more potent antimicrobial therapeutics. | ||
| - | + | Discovery, characterization, and redesign of potent antimicrobial thanatin orthologs from Chinavia ubica and Murgantia histrionica targeting E. coli LptA.,Huynh K, Kibrom A, Donald BR, Zhou P J Struct Biol X. 2023 Jun 13;8:100091. doi: 10.1016/j.yjsbx.2023.100091. , eCollection 2023 Dec. PMID:37416832<ref>PMID:37416832</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8gak" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Chinavia ubica]] | ||
| + | [[Category: Escherichia coli]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Donald B]] | ||
| + | [[Category: Huynh K]] | ||
| + | [[Category: Kibrom A]] | ||
| + | [[Category: Zhou P]] | ||
Revision as of 06:14, 19 July 2023
Crystal Structure of E. coli LptA in complex with Chinavia Ubica Thanatin
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