2JNR

Discovery and optimization of a natural HIV-1 entry inhibitor targeting the gp41 fusion peptide

Summary for 2JNR

• Entry DOI: 10.2210/pdb2jnr/pdb
• NMR Information: BMRB: 15124
• Descriptor: VIR165, ENV polyprotein (2 entities in total)
• Functional Keywords: peptide complex, viral protein
• Biological source: synthetic construct; More
• Total number of polymer chains: 2
• Total formula weight: 4367.16

Authors

Munch, J.,Standker, L.,Adermann, K.,Schulz, A.,Pohlmann, S.,Chaipan, C.,Biet, T.,Peters, T.,Meyer, B.,Wilhelm, D.,Lu, H.,Jing, W.,Jiang, S.,Forssmann, W.,Kirchhoff, F. (deposition date: 2007-02-01, release date: 2007-05-08, Last modification date: 2024-11-20)

Primary citation

Munch, J.,Standker, L.,Adermann, K.,Schulz, A.,Schindler, M.,Chinnadurai, R.,Pohlmann, S.,Chaipan, C.,Biet, T.,Peters, T.,Meyer, B.,Wilhelm, D.,Lu, H.,Jing, W.,Jiang, S.,Forssmann, W.G.,Kirchhoff, F.
Discovery and Optimization of a Natural HIV-1 Entry Inhibitor Targeting the gp41 Fusion Peptide.
Cell(Cambridge,Mass.), 129:263-275, 2007

PubMed Abstract: A variety of molecules in human blood have been implicated in the inhibition of HIV-1. However, it remained elusive which circulating natural compounds are most effective in controlling viral replication in vivo. To identify natural HIV-1 inhibitors we screened a comprehensive peptide library generated from human hemofiltrate. The most potent fraction contained a 20-residue peptide, designated VIRUS-INHIBITORY PEPTIDE (VIRIP), corresponding to the C-proximal region of alpha1-antitrypsin, the most abundant circulating serine protease inhibitor. We found that VIRIP inhibits a wide variety of HIV-1 strains including those resistant to current antiretroviral drugs. Further analysis demonstrated that VIRIP blocks HIV-1 entry by interacting with the gp41 fusion peptide and showed that a few amino acid changes increase its antiretroviral potency by two orders of magnitude. Thus, as a highly specific natural inhibitor of the HIV-1 gp41 fusion peptide, VIRIP may lead to the development of another class of antiretroviral drugs.

PubMed: 17448989
DOI: 10.1016/j.cell.2007.02.042

Experimental method

SOLUTION NMR