1bln
From Proteopedia
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ANTI-P-GLYCOPROTEIN FAB MRK-16
Overview
Monoclonal antibody MRK-16 recognizes a discontinuous extracellular, epitope on the multidrug resistance-associated ATP-binding cassette, transporter, P-glycoprotein. The atomic basis for specificity of this, antibody is of interest because of its potential as a modulator of, P-glycoprotein activity. The crystal structure of Fab MRK-16 is reported, to a resolution of 2.8 A. A structure for a portion of the epitope was, derived by comparison to regions of solved structures with similar primary, sequence. This has permitted a proposal for the mode of binding of the, peptide epitope to the antibody, in which the peptide makes specific, contacts with complementarity-determining regions H1, H2, and H3 from the, heavy chain and L3 from the light chain. These interactions are consistent, with epitope mapping studies and with the observation that MRK-16 is, specific for human class I P-glycoprotein. This result identifies side, chains in MRK-16 that would be amenable to alteration in antibody, engineering experiments to derive improved multidrug resistance inhibitors, for clinical use during chemotherapy. In particular, Arg-H97 contacts both, Glu-746 and Asp-744 of the peptide, Arg-L96 contacts Asp-743, and Thr-H33, interacts with Thr-747. All of these epitope residues were implicated in, mediating specificity by epitope mapping studies.
About this Structure
1BLN is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
Reference
Mode of binding of anti-P-glycoprotein antibody MRK-16 to its antigen. A crystallographic and molecular modeling study., Vasudevan S, Tsuruo T, Rose DR, J Biol Chem. 1998 Sep 25;273(39):25413-9. PMID:9738009
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