Structure of a single-chain Fv fragment of an antibody that inhibits the HIV-1 and HIV-2 proteases.
The monoclonal antibody 1696, which was raised against the HIV-1 protease, inhibits the catalytic activity of the enzyme from both the HIV-1 and HIV-2 strains. The antibody cross-reacts with peptides containing the N-terminus of the enzyme, which is highly conserved between these strains. The crystal structure of a single-chain Fv fragment of 1696 (scFv-1696) in the non-complexed form, solved at 1.7 A resolution, is compared with the previously reported non-complexed Fab-1696 and antigen-bound scFv-1696 structures. Large conformational changes in the third hypervariable region of the heavy chain and differences in relative orientation of the variable domains are observed between the different structures.
Lescar
Julien
J
European Synchrotron Radiation Facility, BP 220, F-38043 Grenoble, France.
Brynda
Jiri
J
Fabry
Milan
M
Horejsi
Magda
M
Rezacova
Pavlina
P
Sedlacek
Juraj
J
Bentley
Graham A
GA
D000911:Antibodies, Monoclonal / Q000737:chemistry; D000941:Antigens / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D016333:HIV Protease / Q000276:immunology / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry; D006860:Hydrogen Bonding; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D007135:Immunoglobulin Variable Region / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008958:Models, Molecular; D055672:Static Electricity
D000911:Antibodies, Monoclonal; D000941:Antigens; D017320:HIV Protease Inhibitors; D007140:Immunoglobulin Fab Fragments; D007135:Immunoglobulin Variable Region; D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease; C065184:p16 protease, Human immunodeficiency virus 2