8qub

From Proteopedia

Hexameric HIV-1 CA in complex with DDD00074110

Structural highlights

8qub is a 1 chain structure with sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.63Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GAG_HV1N5 Matrix protein p17 targets Gag and Gag-Pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus. Also mediates nuclear localization of the preintegration complex. Implicated in the release from host cell mediated by Vpu. Capsid protein p24 forms the conical core of the virus that encapsulates the genomic RNA-nucleocapsid complex. Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. p6-gag plays a role in budding of the assembled particle by interacting with the host class E VPS proteins TSG101 and PDCD6IP/AIP1 (By similarity).

Publication Abstract from PubMed

Identification and assessment of novel targets is essential to combat drug resistance in the treatment of HIV/AIDS. HIV Capsid (HIV-CA), the protein playing a major role in both the early and late stages of the viral life cycle, has emerged as an important target. We have applied an NMR fragment screening platform and identified molecules that bind to the N-terminal domain (NTD) of HIV-CA at a site close to the interface with the C-terminal domain (CTD). Using X-ray crystallography, we have been able to obtain crystal structures to identify the binding mode of these compounds. This allowed for rapid progression of the initial, weak binding, fragment starting points to compounds 37 and 38, which have (19)F-pK(i) values of 5.3 and 5.4 respectively.

Application of an NMR/Crystallography Fragment Screening Platform for the Assessment and Rapid Discovery of New HIV-CA Binding Fragments.,Lang S, Fletcher DA, Petit AP, Luise N, Fyfe P, Zuccotto F, Porter D, Hope A, Bellany F, Kerr C, Mackenzie CJ, Wyatt PG, Gray DW ChemMedChem. 2024 Jul 2;19(13):e202400025. doi: 10.1002/cmdc.202400025. Epub 2024 , May 6. PMID:38581280^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lang S, Fletcher DA, Petit AP, Luise N, Fyfe P, Zuccotto F, Porter D, Hope A, Bellany F, Kerr C, Mackenzie CJ, Wyatt PG, Gray DW. Application of an NMR/Crystallography Fragment Screening Platform for the Assessment and Rapid Discovery of New HIV-CA Binding Fragments. ChemMedChem. 2024 Jul 2;19(13):e202400025. PMID:38581280 doi:10.1002/cmdc.202400025