title: Tubulin aggregation and disaggregation: mediation by two distinct vinblastine-binding sites.
abstract: 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.
mesh_terms: D000818:Animals; D001665:Binding Sites; D001921:Brain; D003078:Colchicine / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D007700:Kinetics; D009994:Osmolar Concentration; D011034:Podophyllotoxin / Q000378:metabolism; D051381:Rats; D013696:Temperature; D014404:Tubulin / Q000378:metabolism*; D014747:Vinblastine / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D014404:Tubulin; D014747:Vinblastine; D011034:Podophyllotoxin; D003078:Colchicine