9CSI

A. baumannii MsbA Bound to Cerastecin Compound 5

これはPDB形式変換不可エントリーです。

9CSI の概要

• エントリーDOI: 10.2210/pdb9csi/pdb
• 分子名称: Lipid A export ATP-binding/permease protein MsbA, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, MONOVACCENIN, ... (6 entities in total)
• 機能のキーワード: msba, antibacterial, inhibitor, cerastecin, antibiotic
• 由来する生物種: Acinetobacter baumannii
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 68559.51

構造登録者

Klein, D.J.,Ishchenko, A.,Soisson, S.,Cheng, R.,Hennig, M. (登録日: 2024-07-23, 公開日: 2024-09-04, 最終更新日: 2024-10-02)

主引用文献

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

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: 39172133
DOI: 10.1021/acs.jmedchem.4c01277

実験手法

X-RAY DIFFRACTION (2.8 Å)