6LMI

Crystal structure of HIV-1 integrase catalytic core domain in complex with 2-(tert-butoxy)-2-[3-(3,4-dihydro-2H-1-benzopyran-6-yl)-6-methanesulfonamido-2,3',4',5-tetramethyl-[1,1'-biphenyl]-4-yl]acetic acid

6LMI の概要

• エントリーDOI: 10.2210/pdb6lmi/pdb
• 分子名称: Integrase catalytic, SULFATE ION, TRIETHYLENE GLYCOL, ... (6 entities in total)
• 機能のキーワード: hydrolase transferase/inhibitor, transferase
• 由来する生物種: Human immunodeficiency virus type 1 group M subtype B (isolate NY5) (HIV-1)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19404.81

構造登録者

Sugiyama, S.,Iwaki, T.,Tamura, Y.,Tomita, K.,Matsuoka, E.,Arita, S.,Seki, T.,Yoshinaga, T.,Kawasuji, T. (登録日: 2019-12-25, 公開日: 2020-09-23, 最終更新日: 2024-11-06)

主引用文献

Sugiyama, S.,Iwaki, T.,Tamura, Y.,Tomita, K.,Matsuoka, E.,Arita, S.,Seki, T.,Yoshinaga, T.,Kawasuji, T.
Discovery of novel integrase-LEDGF/p75 allosteric inhibitors based on a benzene scaffold.
Bioorg.Med.Chem., 28:115643-115643, 2020

PubMed Abstract: We report herein the discovery of novel integrase-LEDGF/p75 allosteric inhibitors (INLAIs) based on a benzene scaffold 3. This scaffold can extend substituents from the C1 position unlike the common pyridine scaffolds 2. Structure-activity relationship studies showed that the sulfonamide linker at the C1 position was important for the antiviral activity. Interaction between sulfonamide and Q95 was observed by X-ray crystallography. Compound 31h showed more potent antiviral activity (EC (NL432) = 3.9 nM) than BI-224436 (EC (NL432) = 56 nM), suggesting the potential of the newly designed scaffold 3.

PubMed: 32773094
DOI: 10.1016/j.bmc.2020.115643

実験手法

X-RAY DIFFRACTION (2.5 Å)