5DVA

Fragments bound to the OXA-48 beta-lactamase: Compound 1

5DVA の概要

• エントリーDOI: 10.2210/pdb5dva/pdb
• 関連するPDBエントリー: 4s2p
• 分子名称: Beta-lactamase, 3-(pyridin-4-yl)benzoic acid, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: hydrolase, inhibitor, complex, fragment, lactamase
• 由来する生物種: Klebsiella pneumoniae
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 114059.84

構造登録者

Lund, B.A.,Christopeit, T.,Leiros, H.-K.S. (登録日: 2015-09-21, 公開日: 2016-06-01, 最終更新日: 2024-01-10)

主引用文献

Lund, B.A.,Christopeit, T.,Guttormsen, Y.,Bayer, A.,Leiros, H.K.
Screening and Design of Inhibitor Scaffolds for the Antibiotic Resistance Oxacillinase-48 (OXA-48) through Surface Plasmon Resonance Screening.
J.Med.Chem., 59:5542-5554, 2016

PubMed Abstract: The spread of antibiotic resistant bacteria is a global threat that shakes the foundations of modern healthcare. β-Lactamases are enzymes that confer resistance to β-lactam antibiotics in bacteria, and there is a critical need for new inhibitors of these enzymes for combination therapy together with an antibiotic. With this in mind, we have screened a library of 490 fragments to identify starting points for the development of new inhibitors of the class D β-lactamase oxacillinase-48 (OXA-48) through surface plasmon resonance (SPR), dose-rate inhibition assays, and X-ray crystallography. Furthermore, we have uncovered structure-activity relationships and used alternate conformations from a crystallographic structure to grow a fragment into a more potent compound with a KD of 50 μM and an IC50 of 18 μM.

PubMed: 27165692
DOI: 10.1021/acs.jmedchem.6b00660

実験手法

X-RAY DIFFRACTION (2.50003891197 Å)