5CPH

Crystal structure of the ATP binding domain of S. aureus GyrB complexed with a fragment

5CPH の概要

• エントリーDOI: 10.2210/pdb5cph/pdb
• 関連するPDBエントリー: 5CTU 5CTX 5CTY 5CUW
• 分子名称: DNA gyrase subunit B, (3E)-3-(pyridin-3-ylmethylidene)-1,3-dihydro-2H-indol-2-one, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: dna gyrase, gyrb, fragment-based screening, structure-based design, isomerase-isomerase inhibitor complex, isomerase/isomerase inhibitor
• 由来する生物種: Staphylococcus aureus
• 細胞内の位置: Cytoplasm : P0A0K8
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48617.99

構造登録者

Andersen, O.A.,Barker, J.,Cheng, R.K.,Kahmann, J.,Felicetti, B.,Wood, M.,Scheich, C.,Mesleh, M.,Cross, J.B.,Zhang, J.,Yang, Q.,Lippa, B.,Ryan, M.D. (登録日: 2015-07-21, 公開日: 2016-02-03, 最終更新日: 2023-09-27)

主引用文献

Mesleh, M.F.,Cross, J.B.,Zhang, J.,Kahmann, J.,Andersen, O.A.,Barker, J.,Cheng, R.K.,Felicetti, B.,Wood, M.,Hadfield, A.T.,Scheich, C.,Moy, T.I.,Yang, Q.,Shotwell, J.,Nguyen, K.,Lippa, B.,Dolle, R.,Ryan, M.D.
Fragment-based discovery of DNA gyrase inhibitors targeting the ATPase subunit of GyrB.
Bioorg.Med.Chem.Lett., 26:1314-1318, 2016

PubMed Abstract: Inhibitors of the ATPase function of bacterial DNA gyrase, located in the GyrB subunit and its related ParE subunit in topoisomerase IV, have demonstrated antibacterial activity. In this study we describe an NMR fragment-based screening effort targeting Staphylococcus aureus GyrB that identified several attractive and novel starting points with good ligand efficiency. Fragment hits were further characterized using NMR binding studies against full-length S. aureus GyrB and Escherichia coli ParE. X-ray co-crystal structures of select fragment hits confirmed binding and suggested a path for medicinal chemistry optimization. The identification, characterization, and elaboration of one of these fragment series to a 0.265 μM inhibitor is described herein.

PubMed: 26786695
DOI: 10.1016/j.bmcl.2016.01.009

実験手法

X-RAY DIFFRACTION (1.2 Å)