ABCB1 p.Gly854Cys
| Predicted by SNAP2: | A: D (71%), C: D (59%), D: D (75%), E: D (80%), F: D (85%), H: D (85%), I: D (80%), K: D (91%), L: D (85%), M: D (85%), N: D (66%), P: D (91%), Q: D (80%), R: D (91%), S: N (72%), T: D (75%), V: D (80%), W: D (91%), Y: D (85%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] A new structural model for P-glycoprotein. J Membr Biol. 1998 Nov 15;166(2):133-47. Jones PM, George AM
A new structural model for P-glycoprotein.
J Membr Biol. 1998 Nov 15;166(2):133-47., 1998-11-15 [PMID:9841738]
Abstract [show]
Multidrug resistance to anti-cancer drugs is a major medical problem. Resistance is manifested largely by the product of the human MDR1 gene, P-glycoprotein, an ABC transporter that is an integral membrane protein of 1280 amino acids arranged into two homologous halves, each comprising 6 putative transmembrane alpha-helices and an ATP binding domain. Despite the plethora of data from site-directed, scanning and domain replacement mutagenesis, epitope mapping and photoaffinity labeling, a clear structural model for P-glycoprotein remains largely elusive. In this report, we propose a new model for P-glycoprotein that is supported by the vast body of previous data. The model comprises 2 membrane-embedded 16-strand beta-barrels, attached by short loops to two 6-helix bundles beneath each barrel. Each ATP binding domain contributes 2 beta-strands and 1 alpha-helix to the structure. This model, together with an analysis of the amino acid sequence alignment of P-glycoprotein isoforms, is used to delineate drug binding and translocation sites. We show that the locations of these sites are consistent with mutational, kinetic and labeling data.
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No. Sentence Comment
149 Six substitutions on the putative extracellular loops between TMs 3 and 4 (T209C, G211C, T215C) and TMs 9 and 10 (S850C, G854C, W855C) unexpectedly failed to react with the labeling reagent.
X
ABCB1 p.Gly854Cys 9841738:149:121
status: NEW