The bioactive Taxol conformation on beta-tubulin: experimental evidence from highly active constrained analogs.
The important anticancer drug Taxol (paclitaxel) binds to tubulin in a stoichiometric ratio and promotes its assembly into microtubules. The conformation of microtubule-bound drug has been the subject of intense study, and various suggestions have been made. In this work we present experimental and theoretical evidence that Taxol adopts a T-shaped conformation when it is bound to tubulin.
Ganesh
Thota
T
Department of Chemistry, M/C 0212, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Guza
Rebecca C
RC
Bane
Susan
S
Ravindra
Rudravajhala
R
Shanker
Natasha
N
Lakdawala
Ami S
AS
Snyder
James P
JP
Kingston
David G I
DG
D045744:Cell Line, Tumor; D003461:Crystallography; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008870:Microtubules / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D014404:Tubulin / Q000737:chemistry*
D014404:Tubulin; D017239:Paclitaxel