1bln

ANTI-P-GLYCOPROTEIN FAB MRK-16ANTI-P-GLYCOPROTEIN FAB MRK-16

Structural highlights 1bln is a 4 chain structure with sequence from Mus musculus. The March 2010 RCSB PDB Molecule of the Month feature on P-glycoprotein by David Goodsell is 10.2210/rcsb_pdb/mom_2010_3. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monoclonal Antibodies 3D structures

spinqualitylabelsall models 1bln, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image