6N3U

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

Summary for 6N3U

• Entry DOI: 10.2210/pdb6n3u/pdb
• EMDB information: 0337
• Descriptor: CTD-SP1 fragment of HIV-1 Gag (1 entity in total)
• Functional Keywords: bevirimat, hiv-1 gag, microed, immature hexagonal lattice, viral protein
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 6
• Total formula weight: 73157.37

Authors

Purdy, M.D.,Shi, D.,Hattne, J.,Chrustowicz, J. (deposition date: 2018-11-16, release date: 2018-12-12, Last modification date: 2023-10-25)

Primary citation

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

Experimental method

ELECTRON CRYSTALLOGRAPHY (2.9 Å)