A salt bridge between an N-terminal coiled coil of gp41 and an antiviral agent targeted to the gp41 cove is important for anti-HIV-1 activity

Citation
Sb. Jiang et Ak. Debnath, A salt bridge between an N-terminal coiled coil of gp41 and an antiviral agent targeted to the gp41 cove is important for anti-HIV-1 activity, BIOC BIOP R, 270(1), 2000, pp. 153-157
Citations number
23
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN journal
0006291X → ACNP
Volume
270
Issue
1
Year of publication
2000
Pages
153 - 157
Database
ISI
SICI code
0006-291X(20000402)270:1<153:ASBBAN>2.0.ZU;2-U
Abstract
HIV-1 envelope glycoprotein transmembrane subunit gp41 play a critical role in the fusion of viral and target cell membranes. The gp41 C-terminal hept ad repeat region interacts with the N-terminal coiled-coil region to form a six-stranded core structure. Peptides derived from gp41 C-terminal heptad repeat region (C-peptides) are potent HIV-1 entry inhibitors by binding to gp41 N-terminal coiled-coil region. Most recently, we have identified two s mall organic compounds that inhibit HIV-1-mediated membrane fusion by block ing the formation of gp41 core. These two active compounds contain both hyd rophobic and acidic groups while the inactive compounds only have hydrophob ic groups. Analysis by computer modeling indicate that the acidic groups in the active compounds can form salt bridge with Lys 574 in the N-terminal c oiled-coil region of gp41. Asp 632 in a C-peptide can also form a salt brid ge with Lys 574. Replacement of Asp 632 with positively charged residues or hydrophobic residues resulted in significant decrease of HIV-1 inhibitory activity. These results suggest that a salt bridge between an N-terminal co iled coil of the gp41 and an antiviral agent targeted to the gp41 core is i mportant for anti-HIV-1 activity. (C) 2000 Academic Press.