1BLN

ANTI-P-GLYCOPROTEIN FAB MRK-16

Summary for 1BLN

• Entry DOI: 10.2210/pdb1bln/pdb
• Descriptor: PROTEIN (MONOCLONAL ANTIBODY MRK-16 (LIGHT CHAIN)), PROTEIN (MONOCLONAL ANTIBODY MRK-16 (HEAVY CHAIN)) (2 entities in total)
• Functional Keywords: immunoglobulin, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 4
• Total formula weight: 93996.76

Authors

Vasudevan, S.,Tsuruo, T.,Rose, D.R. (deposition date: 1998-07-16, release date: 1998-10-28, Last modification date: 2024-10-30)

Primary citation

Vasudevan, S.,Tsuruo, T.,Rose, D.R.
Mode of binding of anti-P-glycoprotein antibody MRK-16 to its antigen. A crystallographic and molecular modeling study.
J.Biol.Chem., 273:25413-25419, 1998

PubMed Abstract: 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.

PubMed: 9738009
DOI: 10.1074/jbc.273.39.25413

Experimental method

X-RAY DIFFRACTION (2.8 Å)