Distinct pose of discodermolide in taxol binding pocket drives a complementary mode of microtubule stabilization.

ABSTRACT: The microtubule cytoskeleton has proven to be an effective target for cancer therapeutics. One class of drugs, known as microtubule stabilizing agents (MSAs), binds to microtubule polymers and stabilizes them against depolymerization. The prototype of this group of drugs, Taxol, is an effective chemotherapeutic agent used extensively in the treatment of human ovarian, breast, and lung carcinomas. Although electron crystallography and photoaffinity labeling experiments determined that the binding site for Taxol is in a hydrophobic pocket in beta-tubulin, little was known about the effects of this drug on the conformation of the entire microtubule. A recent study from our laboratory utilizing hydrogen-deuterium exchange (HDX) in concert with various mass spectrometry (MS) techniques has prov

SUBMITTER: Khrapunovich-Baine M 

PROVIDER: S-EPMC2845443 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature