Summary for 9CSG
| Entry DOI | 10.2210/pdb9csg/pdb |
| Descriptor | Albumin, MYRISTIC ACID, 2-(4-butylbenzene-1-sulfonamido)-5-(4-{3-carboxy-4-[4-(2-methoxyethyl)benzene-1-sulfonamido]anilino}-4-oxobutanamido)benzoic acid, ... (4 entities in total) |
| Functional Keywords | hsa, albumin, msba, antibacterial, inhibitor, cerastecin, antibiotic |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 68422.99 |
| Authors | Hruza, A.,Klein, D.J.,Ishchenko, A. (deposition date: 2024-07-23, release date: 2024-09-04, Last modification date: 2024-10-16) |
| Primary citation | Skudlarek, J.W.,Cooke, A.J.,Mitchell, H.J.,Babaoglu, K.,Shaw, A.W.,Tong, L.,Nomland, A.B.,Labroli, M.,Sha, D.,Mulhearn, J.J.,Wu, C.,Li, S.W.,Beshore, D.C.,Hughes, J.M.E.,Jouffroy, M.,Wang, H.,Balibar, C.J.,Painter, R.E.,Shen, P.,Lange, H.S.,Ishchenko, A.,Chen, Y.T.,Klein, D.J.,Tracy, R.W.,Miller, R.R.,Cabalu, T.D.,Wu, Z.,Leithead, A.,Scapin, G.,Hruza, A.W.,Dzhekieva, L.,Bukhtiyarova, M.,Homsher, M.F.,Xu, M.,Bahnck-Teets, C.,McKenney, D.,Buevich, A.V.,Liu, J.,Zhang, L.K.,Meng, T.,Kelly, T.,DiNunzio, E.,Soisson, S.,Cheng, R.K.Y.,Hennig, M.,Raheem, I.,Walker, S.S. Cerastecin Inhibition of the Lipooligosaccharide Transporter MsbA to Combat Acinetobacter baumannii : From Screening Impurity to In Vivo Efficacy. J.Med.Chem., 67:15620-15675, 2024 Cited by PubMed Abstract: , 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 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 (cerastecin D), which exhibited antibacterial activity in the presence of human serum and a pharmacokinetic profile sufficient to achieve efficacy against in murine septicemia and lung infection models. PubMed: 39172133DOI: 10.1021/acs.jmedchem.4c01277 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.914 Å) |
Structure validation
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