2hrp
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ANTIGEN-ANTIBODY COMPLEX
OverviewOverview
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.
About this StructureAbout this Structure
2HRP is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
Three-dimensional structure of an Fab-peptide complex: structural basis of HIV-1 protease inhibition by a monoclonal antibody., Lescar J, Stouracova R, Riottot MM, Chitarra V, Brynda J, Fabry M, Horejsi M, Sedlacek J, Bentley GA, J Mol Biol. 1997 Apr 18;267(5):1207-22. PMID:9150407
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