期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1976
卷号：73
期号：7
页码：2375-2378
DOI：10.1073/pnas.73.7.2375
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Rat brain tubulin possesses two distinct binding sites for vinblastine per molecule: a high-affinity site with an affinity constant of 6.2 x 10(6) M-1 and a low-affinity site with an affinity constant of 8 x 10(4) M-1. The high-affinity site is labile, with a t1/237 degrees of 3.5 hr, is protected by colchicine, and is unaffected by salt, whereas the low-affinity site is stable but is inhibited by salt. Binding to both sites is rapid. The high-affinity binding constant of vinblastine to tubulin (6.2 x 10(6) M-1) corresponds to the half-maximal concentration of vinblastine needed to prevent polymerization of tubulin in vitro, whereas the low-affinity binding constant (8 x 10(4) M-1) corresponds to the half-maximal concentration of vinblastine required to aggregate tubulin. We conclude that vinblastine binding to the high- and low-affinity sites, respectively, accounts for the depolymerization and aggregation behavior of tubulin.
