STRUCTURAL BASIS OF HIV-1 PROTEASE INHIBITION BY A MONOCLONAL ANTIBODY. Julien Lescar^l, Renata Stouracova^l,2, Marie-Madeleine Riottot^l, Véronique Chitarra^l, Jiri Brynda^l,2, Juraj Sedlacek^2, Graham A. Bentley^l, ¹Unité d'Immunologie Structurale, Institut Pasteur, Paris, ²Department of Gene Manipulation, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague

The crystal structure of the Fab fragment of the anti-HIV-1 protease monoclonal antibody, F11.2.32, has been solved both in the unligated state and as two different complexes with cross-reacting peptide fragments from the viral enzyme corresponding to residues 36-46 and 36-57. This antibody inhibits HIV-1 protease activity with an inhibition constant in the micromolar range. Diffraction measurements made at cryogenic temperatures gave Bragg intensities to 3.0 Å resolution for the free Fab, 2.1 Å resolution for the Fab complexed to peptide 36-46 and 2.6 Å resolution for the Fab complexed to peptide 36-57. Initial models for the three crystal structures were obtained by molecular replacement and refined by simulated anealing.

The structures reveal the peptide to be bound at the centre of the antigen-binding site between residues 38 to 42, which adopt a type II [[beta]] turn conformation. There is only partial correspondence between the structure of this region of the peptide and that of the native antigen.