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Volume 271, Number 25, Issue of June 21, 1996 pp. 14707-14711
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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Localization of the Vinblastine-binding Site on -Tubulin

(Received for publication, January 19, 1996, and in revised form, April 9, 1996)

From the Laboratory of Biochemical Pharmacology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892

A fluorescent vinblastine derivative, vinblastine-4-anthranilate, has been shown to inhibit polymerization of rat brain tubulin (IC₅₀ = 4.8 µM). Binding of the drug to tubulin increases fluorescence intensity, causes a small emission blue shift, and has a quantum yield of 0.037. Fluorescence increases as a function of drug concentration, with a high affinity site and an undetermined number of lower affinity sites. Photolabeling, by exciting the fluorescent drug-tubulin complex at the absorption maximum of anthranilate, yields a covalent adduct confined to -tubulin. Its formation is specific in that it is blocked by maytansine or vinblastine. Tryptic hydrolysis identifies a single fluorescent -peptide coinciding with residues 175-213. The interactions between various ligands at this central portion of -tubulin are discussed.

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