ABCB1 p.Asp744Pro
| Predicted by SNAP2: | A: D (63%), C: D (66%), E: N (66%), F: D (71%), G: N (57%), H: D (71%), I: D (66%), K: D (53%), L: D (71%), M: D (71%), N: N (66%), P: D (53%), Q: D (59%), R: D (71%), S: N (66%), T: N (66%), V: N (53%), W: D (75%), Y: D (71%), |
| Predicted by PROVEAN: | A: D, C: D, E: N, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: N, P: D, Q: N, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Mode of binding of anti-P-glycoprotein antibody MR... J Biol Chem. 1998 Sep 25;273(39):25413-9. Vasudevan S, Tsuruo T, Rose DR
Mode of binding of anti-P-glycoprotein antibody MRK-16 to its antigen. A crystallographic and molecular modeling study.
J Biol Chem. 1998 Sep 25;273(39):25413-9., 1998-09-25 [PMID:9738009]
Abstract [show]
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.
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No. Sentence Comment
201 An alteration of Glu-746 to Lys, as seen in hamster class II Pgp (Table I), would clearly disrupt the interaction with Arg-H97, as would the change of Asp-744 to Pro.
X
ABCB1 p.Asp744Pro 9738009:201:151
status: NEW