1CL7

ANTI HIV1 PROTEASE FAB

Summary for 1CL7

• Entry DOI: 10.2210/pdb1cl7/pdb
• Descriptor: PROTEIN (IGG1 ANTIBODY 1696 (light chain)), PROTEIN (IGG1 ANTIBODY 1696 (variable heavy chain)), PROTEIN (IGG1 ANTIBODY 1696 (constant heavy chain)) (3 entities in total)
• Functional Keywords: fab fragment, cross-reactivity, hiv1 protease, enzyme inhibition, immunoglobulin, immune system
• Biological source: Mus musculus (house mouse); More
• Cellular location: Cell membrane; Single-pass membrane protein (Potential): P01869
• Total number of polymer chains: 3
• Total formula weight: 47660.99

Authors

Lescar, J.,Bentley, G.A. (deposition date: 1999-05-06, release date: 2000-01-12, Last modification date: 2024-11-13)

Primary citation

Lescar, J.,Brynda, J.,Rezacova, P.,Stouracova, R.,Riottot, M.M.,Chitarra, V.,Fabry, M.,Horejsi, M.,Sedlacek, J.,Bentley, G.A.
Inhibition of the HIV-1 and HIV-2 proteases by a monoclonal antibody.
Protein Sci., 8:2686-2696, 1999

PubMed Abstract: The monoclonal antibody 1696, directed against the HIV-1 protease, displays strong inhibitory effects toward the catalytic activity of the enzyme of both the HIV-1 and HIV-2 isolates. This antibody cross-reacts with peptides that include the N-terminus of the enzyme, a region that is well conserved in sequence among different viral strains and which, furthermore, is crucial for homodimerization to the active enzymatic form. This observation, as well as antigen-binding studies in the presence of an active site inhibitor, suggest that 1696 inhibits the HIV protease by destabilizing its active homodimeric form. To characterize further how the antibody 1696 inhibits the HIV-1 and HIV-2 proteases, we have solved the crystal structure of its Fab fragment by molecular replacement and refined it at 3.0 A resolution. The antigen binding site has a deep cavity at its center, which is lined mainly by acidic and hydrophobic residues, and is large enough to accommodate several antigen residues. The structure of the Fab 1696 could form a starting basis for the design of alternative HIV protease-inhibiting molecules of broad specificity.

PubMed: 10631984

Experimental method

X-RAY DIFFRACTION (3 Å)