X-ray structure of the uncomplexed anti-tumor antibody BR96 and comparison with its antigen-bound form.
The X-ray structure of the uncomplexed human chimeric Fab' of the anti-tumor antibody BR96 has been determined at 2.6 A resolution. The structure has been compared with Lewis Y antigen-complexed structures of BR96 which were determined previously. The comparison reveals segmental motions and/or conformational rearrangements of three CDR loops (L1, L3, and H2), whereas CDR H3 does not undergo changes upon complexation despite its significant main-chain contacts to the carbohydrate antigen. In light of the uncomplexed chimeric Fab' structure reported here, the previously observed high mobility of the CL:CH1 domains of the complexed chimeric BR96 Fab is rationalized as a "swinging" motion approximately about the axis of the elbow bend.
Sheriff
S
S
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA.
Chang
C Y
CY
Jeffrey
P D
PD
Bajorath
J
J
D000818:Animals; D000912:Antibodies, Neoplasm / Q000737:chemistry* / Q000276:immunology; D000937:Antigen-Antibody Reactions; D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000276:immunology; D002240:Carbohydrate Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000276:immunology; D007983:Lewis Blood Group Antigens / Q000276:immunology; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D007140:Immunoglobulin Fab Fragments; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D011993:Recombinant Fusion Proteins