9D8T

Crystal structure of KPC-2 complexed with compound 16

これはPDB形式変換不可エントリーです。

9D8T の概要

• エントリーDOI: 10.2210/pdb9d8t/pdb
• 関連するPDBエントリー: 9D2U 9D54 9D5Q 9D5R
• 分子名称: Carbapenem-hydrolyzing beta-lactamase KPC, SULFATE ION, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: inhibitor, beta-lactamase, complex, kpc, hydrolase
• 由来する生物種: Klebsiella pneumoniae
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31491.06

構造登録者

Jacobs, L.M.C.,Chen, Y. (登録日: 2024-08-20, 公開日: 2025-09-03, 最終更新日: 2026-03-25)

主引用文献

Jacobs, L.M.C.,Jaishankar, P.,Zheng, J.,Hantz, E.R.,Lee, I.,Narramneni, K.,Poore, N.,Torres, N.,Jackson, J.K.,Williams, O.,Darch, S.E.,Shaw, L.N.,Chen, Y.,Renslo, A.R.
Structure-Based Design of Reversible, Quinoline-2(1 H )‐one Inhibitors of Serine- and Metallo-Carbapenemases.
Acs Omega, 11:15316-15327, 2026

PubMed Abstract: Carbapenems are essential β-lactam antibiotics whose clinical utility is now threatened by emerging carbapenemases, including the Class A serine β-lactamase KPC-2 and the Class B metallo-β-lactamase NDM-1. Here, we describe a comprehensive, structure-based assessment of active-site binding determinants for KPC-2 and NDM-1 in the context of reversible, noncovalent inhibition by a quinoline-2-(1)-one phosphonate scaffold. Systematic substitution of the scaffold core revealed the N1 and C7 positions as most tolerant of diverse substitution, while the less tolerant C3 and C6 positions nevertheless drive affinity and binding mode when modified with a C3-methyl or C6-fluoro substituent, respectively. We also describe biophysical and computational studies aimed at determining the pharmacological significance of the 2:1 ligand binding stoichiometry observed in several NDM-1 complex structures, concluding that only one of these binding events is relevant for potent NDM-1 inhibition. Although the current inhibitors lack significant whole-cell activity, the structural and biochemical findings described provide valuable information for the targeting of evolutionarily and mechanistically diverse carbapenemases.

PubMed: 41835567
DOI: 10.1021/acsomega.5c12676

実験手法

X-RAY DIFFRACTION (1.97 Å)