ABCMdb

PMID: 25068895

Prajapati R, Sangamwar AT
Translocation mechanism of P-glycoprotein and conformational changes occurring at drug-binding site: Insights from multi-targeted molecular dynamics.
Biochim Biophys Acta. 2014 Nov;1838(11):2882-98. doi: 10.1016/j.bbamem.2014.07.018. Epub 2014 Jul 25., [PubMed]

Sentences

No. Mutations Sentence Comment

259 ABCB1 p.Arg262Thr ABCB1 p.Tyr1087Asp (A) angular rotation between Cb1;-atoms of ICH2, ICH3 and NBD2 residues Arg 262-Thr 263-Val264 (black), Asp 805-Asp 806-Pro 807 (green) and Tyr 1087-Asp 1088-Pro 1089 (red), respectively. Login to comment 260 ABCB1 p.Arg905Thr (B) angular rotation between Cb1;-atoms of ICH4, ICH1 and NBD1 residues Arg 905-Thr 906-Val 907 (black), Asp 164-Val 165-His 166 (red) and Tyr 444-Asp 445-Pro 446 (green), respectively. Login to comment 325 ABCB1 p.Asn820Cys In another recent experiment [69], Loo and Clarke tested the effects of cross-linking mutant L175C (ICL1)/N820C (ICL3) to determine the distance between N-terminal and C-terminal half of P-gp that show high or low ATPase activity. Login to comment 326 ABCB1 p.Asn820Cys They observed that there was over 10 fold increase in basal ATPase activity when L175C was linked to N820C with cross-linkers predicted to span a distance of less than 20 &#c5;, and predicted that the ATPase activation switch appears to be turned on or off when this distance is less than or greater than 20 &#c5;, respectively. Login to comment 462 ABCB1 p.Trp803Cys In this experiment Loo and Clarke cross-linked A259C (ICH2) and W803C (ICH3) that resulted in loss of P-gp ATPase activity. Login to comment