2HRP

ANTIGEN-ANTIBODY COMPLEX

Summary for 2HRP

• Entry DOI: 10.2210/pdb2hrp/pdb
• Descriptor: MONOCLONAL ANTIBODY F11.2.32, HIV-1 PROTEASE PEPTIDE, ... (4 entities in total)
• Functional Keywords: fab fragment, cross-reactivity, hiv1 protease, enzyme inhibition, complex (immunoglobulin-peptide), complex (immunoglobulin-peptide) complex, complex (immunoglobulin/peptide)
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 6
• Total formula weight: 99040.56

Authors

Lescar, J.,Bentley, G.A. (deposition date: 1996-12-27, release date: 1997-12-31, Last modification date: 2024-10-23)

Primary citation

Lescar, J.,Stouracova, R.,Riottot, M.M.,Chitarra, V.,Brynda, J.,Fabry, M.,Horejsi, M.,Sedlacek, J.,Bentley, G.A.
Three-dimensional structure of an Fab-peptide complex: structural basis of HIV-1 protease inhibition by a monoclonal antibody.
J.Mol.Biol., 267:1207-1222, 1997

PubMed Abstract: F11.2.32, a monoclonal antibody raised against HIV-1 protease (Kd = 5 nM), which inhibits proteolytic activity of the enzyme (K(inh) = 35(+/-3)nM), has been studied by crystallographic methods. The three-dimensional structure of the complex between the Fab fragment and a synthetic peptide, spanning residues 36 to 46 of the protease, has been determined at 2.2 A resolution, and that of the Fab in the free state has been determined at 2.6 A resolution. The refined model of the complex reveals ten well-ordered residues of the peptide (P36 to P45) bound in a hydrophobic cavity at the centre of the antigen-binding site. The peptide adopts a beta hairpin-like structure in which residues P38 to P42 form a type II beta-turn conformation. An intermolecular antiparallel beta-sheet is formed between the peptide and the CDR3-H loop of the antibody; additional polar interactions occur between main-chain atoms of the peptide and hydroxyl groups from tyrosine residues protruding from CDR1-L and CDR3-H. Three water molecules, located at the antigen-antibody interface, mediate polar interactions between the peptide and the most buried hypervariable loops, CDR3-L and CDR1-H. A comparison between the free and complexed Fab fragments shows that significant conformational changes occur in the long hypervariable regions, CDR1-L and CDR3-H, upon binding the peptide. The conformation of the bound peptide, which shows no overall structural similarity to the corresponding segment in HIV-1 protease, suggests that F11.2.32 might inhibit proteolysis by distorting the native structure of the enzyme.

PubMed: 9150407
DOI: 10.1006/jmbi.1997.0950

Experimental method

X-RAY DIFFRACTION (2.2 Å)