ABCMdb

PMID: 16565061

Omote H, Al-Shawi MK
Interaction of transported drugs with the lipid bilayer and P-glycoprotein through a solvation exchange mechanism.
Biophys J. 2006 Jun 1;90(11):4046-59. Epub 2006 Mar 24., [PubMed]

Sentences

No. Mutations Sentence Comment

9 ABCB1 p.Gly185Val A molecular basis for the improved colchicine transport efficiency by the much-studied colchicine-resistance G185V mutant human P-glycoprotein is also provided. Login to comment 221 ABCB1 p.Gly185Val The G185V mutation suppresses this effect by increasing the intrinsic rate of transport to the expected one (Fig. 9). Login to comment 222 ABCB1 p.Gly185Val It should be emphasized that G185V P-glycoprotein does not change the intrinsic drug transport rate or drug binding characteristics of all drugs but only a limited subset such as colchicine and etoposide (33). Login to comment 224 ABCB1 p.Gly185Val Thus, the G185V mutation distorts the binding site for colchicine while leaving binding sites of other drugs intact. Login to comment 225 ABCB1 p.Gly185Val Binding of colchicine to WT and G185V P-glycoproteins were characterized by van`t Hoff analysis by methods previously described (52). Login to comment 228 ABCB1 p.Gly185Val The corresponding values for colchicine binding to G185V P-glycoprotein were ÿ191.4, ÿ176.9, and ÿ14.5 kJ molÿ1 , respectively. Login to comment 229 ABCB1 p.Gly185Val Here the net driving force for colchicine binding to G185V P-glycoprotein was through favorable noncovalent interactions (H-bonds) compensated somewhat by a large unfavorable entropy term. Login to comment 246 ABCB1 p.Gly185Val The G185V mutation modified the colchicine binding site in such a fashion as to reduce the contribution of nonpolar interactions. Login to comment 248 ABCB1 p.Gly185Val These factors improve the colchicine transport rate and coupling efficiency of the G185V mutation as previously described (33). Login to comment 315 ABCB1 p.Gly185Val In Results and Fig. 9 we demonstrate that G185V P-glycoprotein interacts with colchicine in a manner that removes an overabundance of nonpolar van der Waals interactions while satisfying the available H-bond acceptors. Login to comment 375 ABCB1 p.Gly185Val This was the case for the improved transport of colchicine by the G185V mutation (33) (Fig. 9). Login to comment