Structural insight into substrate and inhibitor discrimination by human P-glycoprotein

See allHide authors and affiliations

Science  15 Feb 2019:
Vol. 363, Issue 6428, pp. 753-756
DOI: 10.1126/science.aav7102

You are currently viewing the editor's summary.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

To transport or not to transport

Therapeutic drug delivery into cells is complicated by membrane proteins like ABCB1 (also termed P-glycoprotein) that shuttle diverse compounds out of cells. Alam et al. determined high-resolution cryo–electron microscopy structures of ABCB1 bound either to a substrate, the cancer drug Taxol, or to the ABCB1 inhibitor zosuquidar. The conformational changes that facilitate drug transport are caused by hydrolysis of adenosine triphosphate (ATP). The structures show that, although Taxol and zosquidar bind to the same site, subtle structural differences lead to altered conformations of the nucleotide binding domains that are responsible for ATP hydrolysis.

Science, this issue p. 753