+検索条件
-Structure paper
タイトル | MicroED structures of HIV-1 Gag CTD-SP1 reveal binding interactions with the maturation inhibitor bevirimat. |
---|---|
ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 115, Issue 52, Page 13258-13263, Year 2018 |
掲載日 | 2018年12月26日 |
著者 | Michael D Purdy / Dan Shi / Jakub Chrustowicz / Johan Hattne / Tamir Gonen / Mark Yeager / |
PubMed 要旨 | 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 ...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. |
リンク | Proc Natl Acad Sci U S A / PubMed:30530702 / PubMed Central |
手法 | EM (電子線結晶学) |
解像度 | 2.9 - 3.0 Å |
構造データ | |
由来 |
|
キーワード | VIRAL PROTEIN / Bevirimat / HIV-1 Gag / MicroED / Immature Hexagonal Lattice |