6N3U

MicroED Structure of the CTD-SP1 fragment of HIV-1 Gag with bound maturation inhibitor Bevirimat.

6N3U の概要

• エントリーDOI: 10.2210/pdb6n3u/pdb
• EMDBエントリー: 0337
• 分子名称: CTD-SP1 fragment of HIV-1 Gag (1 entity in total)
• 機能のキーワード: bevirimat, hiv-1 gag, microed, immature hexagonal lattice, viral protein
• 由来する生物種: Human immunodeficiency virus 1
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 73157.37

構造登録者

Purdy, M.D.,Shi, D.,Hattne, J.,Chrustowicz, J. (登録日: 2018-11-16, 公開日: 2018-12-12, 最終更新日: 2023-10-25)

主引用文献

Purdy, M.D.,Shi, D.,Chrustowicz, J.,Hattne, J.,Gonen, T.,Yeager, M.
MicroED structures of HIV-1 Gag CTD-SP1 reveal binding interactions with the maturation inhibitor bevirimat.
Proc. Natl. Acad. Sci. U.S.A., 115:13258-13263, 2018

PubMed Abstract: HIV-1 protease (PR) cleavage of the Gag polyprotein triggers the assembly of mature, infectious particles. Final cleavage of Gag occurs at the junction helix between the capsid protein CA and the SP1 spacer peptide. Here we used MicroED to delineate the binding interactions of the maturation inhibitor bevirimat (BVM) using very thin frozen-hydrated, 3D microcrystals of a CTD-SP1 Gag construct with and without bound BVM. The 2.9-Å MicroED structure revealed that a single BVM molecule stabilizes the six-helix bundle via both electrostatic interactions with the dimethylsuccinyl moiety and hydrophobic interactions with the pentacyclic triterpenoid ring. These results provide insight into the mechanism of action of BVM and related maturation inhibitors that will inform further drug discovery efforts. This study also demonstrates the capabilities of MicroED for structure-based drug design.

PubMed: 30530702
DOI: 10.1073/pnas.1806806115

実験手法

ELECTRON CRYSTALLOGRAPHY (2.9 Å)