6TT8

Haddock model of NDM-1/morin complex

6TT8 の概要

• エントリーDOI: 10.2210/pdb6tt8/pdb
• NMR情報: BMRB: 34471
• 分子名称: Metallo beta lactamase NDM-1, ZINC ION, 2-[2,4-bis(oxidanyl)phenyl]-3,5,7-tris(oxidanyl)chromen-4-one (3 entities in total)
• 機能のキーワード: complex, inhibitor, morin, new-delhi metallo-beta-lactamase-1, haddock, antimicrobial resistance, metal binding protein
• 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: 24408.01

構造登録者

Riviere, G.,Oueslati, S.,Gayral, M.,Crechet, J.B.,Nhiri, N.,Jacquet, E.,Cintrat, J.C.,Giraud, F.,van Heijenoort, C.,Lescop, E.,Pethe, S.,Iorga, B.I.,Naas, T.,Guittet, E.,Morellet, N. (登録日: 2019-12-25, 公開日: 2021-01-13, 最終更新日: 2024-05-15)

主引用文献

Riviere, G.,Oueslati, S.,Gayral, M.,Crechet, J.B.,Nhiri, N.,Jacquet, E.,Cintrat, J.C.,Giraud, F.,van Heijenoort, C.,Lescop, E.,Pethe, S.,Iorga, B.I.,Naas, T.,Guittet, E.,Morellet, N.
NMR Characterization of the Influence of Zinc(II) Ions on the Structural and Dynamic Behavior of the New Delhi Metallo-beta-Lactamase-1 and on the Binding with Flavonols as Inhibitors.
Acs Omega, 5:10466-10480, 2020

PubMed Abstract: New Delhi metallo-β-lactamase-1 (NDM-1) has recently emerged as a global threat because of its ability to confer resistance to all common β-lactam antibiotics. Understanding the molecular basis of β-lactam hydrolysis by NDM is crucial for designing NDM inhibitors or β-lactams resistant to their hydrolysis. In this study, for the first time, NMR was used to study the influence of Zn(II) ions on the dynamic behavior of NDM-1. Our results highlighted that the binding of Zn(II) in the NDM-1 active site induced several structural and dynamic changes on active site loop 2 (ASL2) and L9 loops and on helix α2. We subsequently studied the interaction of several flavonols: morin, quercetin, and myricetin were identified as natural and specific inhibitors of NDM-1. Quercetin conjugates were also synthesized in an attempt to increase the solubility and bioavailability. Our NMR investigations on NDM-1/flavonol interactions highlighted that both Zn(II) ions and the residues of the NDM-1 ASL1, ASL2, and ASL4 loops are involved in the binding of flavonols. This is the first NMR interaction study of NDM-1/inhibitors, and the models generated using HADDOCK will be useful for the rational design of more active inhibitors, directed against NDM-1.

PubMed: 32426604
DOI: 10.1021/acsomega.0c00590

実験手法

SOLUTION NMR