6R1P

EthR ligand complex

6R1P の概要

• エントリーDOI: 10.2210/pdb6r1p/pdb
• 分子名称: HTH-type transcriptional regulator EthR, 2-[2-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-1,2,3-triazol-1-yl]ethyl]-6-methyl-1~{H}-pyrimidin-4-one (3 entities in total)
• 機能のキーワード: transcriptional regulator tuberculosis tetr inhibitor, dna binding protein
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24121.05

構造登録者

Pohl, E.,Tatum, N. (登録日: 2019-03-14, 公開日: 2020-02-19, 最終更新日: 2024-01-24)

主引用文献

Tatum, N.J.,Duarte, F.,Kamerlin, S.C.L.,Pohl, E.
Relative Binding Energies Predict Crystallographic Binding Modes of Ethionamide Booster Lead Compounds.
J Phys Chem Lett, 10:2244-2249, 2019

PubMed Abstract: Transcriptional repressor EthR from Mycobacterium tuberculosis is a valuable target for antibiotic booster drugs. We previously reported a virtual screening campaign to identify EthR inhibitors for development. Two ligand binding orientations were often proposed, though only the top scoring pose was utilized for filtering of the large data set. We obtained biophysically validated hits, some of which yielded complex crystal structures. In some cases, the crystallized binding mode and top scoring mode agree, while for others an alternate ligand binding orientation was found. In this contribution, we combine rigid docking, molecular dynamics simulations, and the linear interaction energy method to calculate binding free energies and derive relative binding energies for a number of EthR inhibitors in both modes. This strategy allowed us to correctly predict the most favorable orientation. Therefore, this widely applicable approach will be suitable to triage multiple binding modes within EthR and other potential drug targets with similar characteristics.

PubMed: 30965004
DOI: 10.1021/acs.jpclett.9b00741

実験手法

X-RAY DIFFRACTION (1.8 Å)