PMID: 22380603

Sager G, Orvoll EO, Lysaa RA, Kufareva I, Abagyan R, Ravna AW
Novel cGMP efflux inhibitors identified by virtual ligand screening (VLS) and confirmed by experimental studies.
J Med Chem. 2012 Apr 12;55(7):3049-57. Epub 2012 Mar 20., [PubMed]
Sentences
No. Mutations Sentence Comment
85 ABCB1 p.Leu65Cys
X
ABCB1 p.Leu65Cys 22380603:85:200
status: NEW
view ABCB1 p.Leu65Cys details
ABCB1 p.Ile306Cys
X
ABCB1 p.Ile306Cys 22380603:85:220
status: NEW
view ABCB1 p.Ile306Cys details
 This is in accordance with a study on ABCB1 where cysteine-scanning mutagenesis and reaction with a methanethiosulfonate (MTS) thiol reactive analogue of verapamil (MTS verapamil) showed that mutants Leu65Cys (TMH1) and Ile306Cys (TMH5) modified with MTS verapamil have slightly different characteristics, indicating that the bound verapamil molecules in these mutants have different orientations and that the protein can function quite well with the substrate bound in different orientations.28 Theoretically, even though 10 different conformations of each ligand were evaluated by ICM during VLS, focusing on only the ligand orientation with best score may lead to missing out better inhibitors oriented in a pose yielding a poorer score. Login to comment