7ZBV

Crystal structure of the peptidase domain of collagenase G from Clostridium histolyticum in complex with a diphosphonate-based inhibitor

7ZBV の概要

• エントリーDOI: 10.2210/pdb7zbv/pdb
• 関連するPDBエントリー: 2y6i
• 分子名称: Collagenase ColG, ZINC ION, [6,7-bis(chloranyl)-3-phosphono-quinoxalin-2-yl]phosphonic acid, ... (6 entities in total)
• 機能のキーワード: collagenase, diphosphonate, colg, inhibitor, complex, hydrolase
• 由来する生物種: Hathewaya histolytica
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 48831.50

構造登録者

Schoenauer, E.,Brandstetter, H. (登録日: 2022-03-24, 公開日: 2022-11-09, 最終更新日: 2024-01-31)

主引用文献

Alhayek, A.,Abdelsamie, A.S.,Schonauer, E.,Camberlein, V.,Hutterer, E.,Posselt, G.,Serwanja, J.,Blochl, C.,Huber, C.G.,Haupenthal, J.,Brandstetter, H.,Wessler, S.,Hirsch, A.K.H.
Discovery and Characterization of Synthesized and FDA-Approved Inhibitors of Clostridial and Bacillary Collagenases.
J.Med.Chem., 65:12933-12955, 2022

PubMed Abstract: In view of the worldwide antimicrobial resistance (AMR) threat, new bacterial targets and anti-infective agents are needed. Since important roles in bacterial pathogenesis have been demonstrated for the collagenase H and G (ColH and ColG) from , collagenase Q1 and A (ColQ1 and ColA) from represent attractive antivirulence targets. Furthermore, repurposing FDA-approved drugs may assist to tackle the AMR crisis and was addressed in this work. Here, we report on the discovery of two potent and chemically stable bacterial collagenase inhibitors: synthesized and FDA-approved diphosphonates and hydroxamates. Both classes showed high activity against the clostridial and bacillary collagenases. The potent diphosphonates reduced -mediated detachment and death of cells and larvae. The hydroxamates were also tested in a similar manner; they did not have an effect in infection models. This might be due to their fast binding kinetics to bacterial collagenases.

PubMed: 36154055
DOI: 10.1021/acs.jmedchem.2c00785

実験手法

X-RAY DIFFRACTION (1.95 Å)