7RSX

HIV-1 gp120 complex with CJF-III-049-S

This is a non-PDB format compatible entry.

Summary for 7RSX

• Entry DOI: 10.2210/pdb7rsx/pdb
• Descriptor: ENVELOPE GLYCOPROTEIN GP120, 2-acetamido-2-deoxy-beta-D-glucopyranose, N~1~-{(1R,2R,3S)-2-(carbamimidamidomethyl)-3-[(3S)-3,4-dihydroxybutyl]-5-[(methylamino)methyl]-2,3-dihydro-1H-inden-1-yl}-N~2~-(4-chloro-3-fluorophenyl)ethanediamide, ... (4 entities in total)
• Functional Keywords: hiv-1 gp120, inhibitor, viral protein
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 4
• Total formula weight: 169147.37

Authors

Liang, S.,Hendrickson, W.A. (deposition date: 2021-08-12, release date: 2022-06-08, Last modification date: 2024-10-30)

Primary citation

Fritschi, C.J.,Liang, S.,Mohammadi, M.,Anang, S.,Moraca, F.,Chen, J.,Madani, N.,Sodroski, J.G.,Abrams, C.F.,Hendrickson, W.A.,Smith 3rd, A.B.
Identification of gp120 Residue His105 as a Novel Target for HIV-1 Neutralization by Small-Molecule CD4-Mimics.
Acs Med.Chem.Lett., 12:1824-1831, 2021

PubMed Abstract: The design and synthesis of butyl chain derivatives at the indane ring 3-position of our lead CD4-mimetic compound BNM-III-170 that inhibits human immunodeficiency virus (HIV-1) infection are reported. Optimization efforts were guided by crystallographic and computational analysis of the small-molecule ligands of the Phe43 cavity of the envelope glycoprotein gp120. Biological evaluation of - revealed that members of this series of CD4-mimetic compounds are able to inhibit HIV-1 viral entry into target cells more potently and with greater breadth compared to BNM-III-170. Crystallographic analysis of the binding pocket of , , and revealed a novel hydrogen bonding interaction between His105 and a primary hydroxyl group on the butyl side chain. Further optimization of this interaction with the His105 residue holds the promise of more potent CD4-mimetic compounds.

PubMed: 34795873
DOI: 10.1021/acsmedchemlett.1c00437

Experimental method

X-RAY DIFFRACTION (2.75 Å)