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
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.