View source for 9csg


==Human Serum Albumin Bound to Cerastecin Compound 5e==
<StructureSection load='9csg' size='340' side='right'caption='[[9csg]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9csg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9CSG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9CSG 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]] 1.914&#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=9csg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9csg OCA], [https://pdbe.org/9csg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9csg RCSB], [https://www.ebi.ac.uk/pdbsum/9csg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9csg ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ALBU_HUMAN ALBU_HUMAN] Defects in ALB are a cause of familial dysalbuminemic hyperthyroxinemia (FDH) [MIM:[https://omim.org/entry/103600 103600]. FDH is a form of euthyroid hyperthyroxinemia that is due to increased affinity of ALB for T(4). It is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasian population.<ref>PMID:8048949</ref> <ref>PMID:7852505</ref> <ref>PMID:9329347</ref> <ref>PMID:9589637</ref> 
== Function ==
[https://www.uniprot.org/uniprot/ALBU_HUMAN ALBU_HUMAN] Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.<ref>PMID:19021548</ref> 
<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 9csg" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hruza A]]
[[Category: Ishchenko A]]
[[Category: Klein DJ]]