Pironetin reacts covalently with cysteine-316 of α-tubulin to destabilize microtubule.

ABSTRACT: Molecules that alter the normal dynamics of microtubule assembly and disassembly include many anticancer drugs in clinical use. So far all such therapeutics target β-tubulin, and structural biology has explained the basis of their action and permitted design of new drugs. However, by shifting the profile of β-tubulin isoforms, cancer cells become resistant to treatment. Compounds that bind to α-tubulin are less well characterized and unexploited. The natural product pironetin is known to bind to α-tubulin and is a potent inhibitor of microtubule polymerization. Previous reports had identified that pironetin reacts with lysine-352 residue however analogues designed on this model had much lower potency, which was difficult to explain, hindering further development. We report crystallographic

SUBMITTER: Yang J 

PROVIDER: S-EPMC4931326 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature