View source for 9csi


==A. baumannii MsbA Bound to Cerastecin Compound 5==
<StructureSection load='9csi' size='340' side='right'caption='[[9csi]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9csi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Acinetobacter_baumannii Acinetobacter baumannii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9CSI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9CSI 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]] 2.8&#8491;</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=9csi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9csi OCA], [https://pdbe.org/9csi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9csi RCSB], [https://www.ebi.ac.uk/pdbsum/9csi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9csi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A6F8TGG1_ACIBA A0A6F8TGG1_ACIBA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Acinetobacter baumannii, a commonly multidrug-resistant Gram-negative bacterium responsible for large numbers of bloodstream and lung infections worldwide, is increasingly difficult to treat and constitutes a growing threat to human health. Structurally novel antibacterial chemical matter that can evade existing resistance mechanisms is essential for addressing this critical medical need. Herein, we describe our efforts to inhibit the essential A. baumannii lipooligosaccharide (LOS) ATP-binding cassette (ABC) transporter MsbA. An unexpected impurity from a phenotypic screening was optimized as a series of dimeric compounds, culminating with 1 (cerastecin D), which exhibited antibacterial activity in the presence of human serum and a pharmacokinetic profile sufficient to achieve efficacy against A. baumannii in murine septicemia and lung infection models.

Cerastecin Inhibition of the Lipooligosaccharide Transporter MsbA to Combat Acinetobacter baumannii: From Screening Impurity to In Vivo Efficacy.,Skudlarek JW, Cooke AJ, Mitchell HJ, Babaoglu K, Shaw AW, Tong L, Nomland AB, Labroli M, Sha D, Mulhearn JJ, Wu C, Li SW, Beshore DC, Hughes JME, Jouffroy M, Wang H, Balibar CJ, Painter RE, Shen P, Lange HS, Ishchenko A, Chen YT, Klein DJ, Tracy RW, Miller RR, Cabalu TD, Wu Z, Leithead A, Scapin G, Hruza AW, Dzhekieva L, Bukhtiyarova M, Homsher MF, Xu M, Bahnck-Teets C, McKenney D, Buevich AV, Liu J, Zhang LK, Meng T, Kelly T, DiNunzio E, Soisson S, Cheng RKY, Hennig M, Raheem I, Walker SS J Med Chem. 2024 Aug 22. doi: 10.1021/acs.jmedchem.4c01277. PMID:39172133<ref>PMID:39172133</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9csi" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Acinetobacter baumannii]]
[[Category: Large Structures]]
[[Category: Cheng R]]
[[Category: Hennig M]]
[[Category: Ishchenko A]]
[[Category: Klein DJ]]
[[Category: Soisson S]]