4MJP

E. coli sliding clamp in complex with (R)-Vedaprofen

4MJP の概要

• エントリーDOI: 10.2210/pdb4mjp/pdb
• 関連するPDBエントリー: 4MJQ 4MJR
• 分子名称: DNA polymerase III subunit beta, DI(HYDROXYETHYL)ETHER, TRIETHYLENE GLYCOL, ... (7 entities in total)
• 機能のキーワード: poliii beta, sliding clamp, dnan, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cytoplasm: P0A988
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 82202.42

構造登録者

Yin, Z.,Oakley, A.J. (登録日: 2013-09-04, 公開日: 2013-09-18, 最終更新日: 2023-09-20)

主引用文献

Yin, Z.,Wang, Y.,Whittell, L.R.,Jergic, S.,Liu, M.,Harry, E.,Dixon, N.E.,Kelso, M.J.,Beck, J.L.,Oakley, A.J.
DNA replication is the target for the antibacterial effects of nonsteroidal anti-inflammatory drugs.
Chem.Biol., 21:481-487, 2014

PubMed Abstract: Evidence suggests that some nonsteroidal anti-inflammatory drugs (NSAIDs) possess antibacterial properties with an unknown mechanism. We describe the in vitro antibacterial properties of the NSAIDs carprofen, bromfenac, and vedaprofen, and show that these NSAIDs inhibit the Escherichia coli DNA polymerase III β subunit, an essential interaction hub that acts as a mobile tether on DNA for many essential partner proteins in DNA replication and repair. Crystal structures show that the three NSAIDs bind to the sliding clamp at a common binding site required for partner binding. Inhibition of interaction of the clamp loader and/or the replicative polymerase α subunit with the sliding clamp is demonstrated using an in vitro DNA replication assay. NSAIDs thus present promising lead scaffolds for novel antibacterial agents targeting the sliding clamp.

PubMed: 24631121
DOI: 10.1016/j.chembiol.2014.02.009

実験手法

X-RAY DIFFRACTION (1.855 Å)