Does colchicine bind to tubulin?
Colchicine exerts its biological effects through binding to the soluble tubulin heterodimer, the major component of the microtubule. The colchicine-binding abilities of tubulins from a variety of sources are summarized, and the mechanism of colchicine binding to brain tubulin is explored in depth.
Is colchicine a microtubule inhibitor?
Colchicine is a Colchicum autumnale plant alkaloid that inhibits polymerization of microtubules, a process that is believed to be required for collagen secretion. Thus, this compound is believed to work as an antifibrotic compound by preventing collagen secretion and deposition.
What do tubulin inhibitors do?
Microtubule inhibitors (MTI) such as taxanes, vinca alkaloids, and epothilones stabilize or destabilize microtubules, thereby suppressing microtubule dynamics required for proper mitotic function, effectively blocking cell cycle progression and resulting in apoptosis.
Why should the binding of colchicine to tubulin molecules interfere with the formation of microtubules?
Colchicine binding to β-tubulin results in curved tubulin dimer and prevents it to adopt a straight structure, due to a steric clash between colchicine and α-tubulin, which inhibits microtubule assembly (3).
How does colchicine work in mitosis?
The alkaloid drug, colchicine, extracted from the corm of the autumn crocus (Colchicum autumnale), arrests mitosis in metaphase by interfering with the formation of spindle fibrils, thereby retarding the division of the centromeres and preventing division of the centrioles.
How does colchicine inhibit microtubule polymerization?
Colchicine is a classical anti-mitotic drug which blocks mitotic cells in metaphase. It binds to soluble tubulin to form tubulin-colchicine complexes in a poorly reversible manner, which then binds to the ends of microtubules to prevent the elongation of the microtubule polymer.
What effect does colchicine have on mitosis?
The most striking effect of cold and of colchicine is the arrest of mitosis when the chromosomes have reached metaphase spiralization. This arrest leads to an accumulation of cells at this stage.
What does colchicine do to the body?
Colchicine works by decreasing swelling and lessening the build up of uric acid crystals that cause pain in the affected joint(s). This medication is also used to prevent attacks of pain in the abdomen, chest, or joints caused by a certain inherited disease (familial Mediterranean fever).
How do colchicine binding site inhibitors work?
Colchicine binding site inhibitors (CBSI) exert their biological effects by inhibiting tubulin assembly and suppressing microtubule formation. A large number of molecules interacting with the colchicine binding site have been designed and synthesized with significant structural diversity.
What is the role of colchicine in tubulin polymerization?
The colchicine binding site is one of the most important pockets for potential tubulin polymerization destabilizers. Colchicine binding site inhibitors (CBSI) exert their biological effects by inhibiting tubulin assembly and suppressing microtubule formation.
Is colchicine a microtubule interfering agent?
Indeed, vinblastine prevents self-association of tubulin by interacting at the interface between two αβ–tubulin heterodimers (2). The fourth group of microtubule interfering agents is represented by colchicine, which also induces microtubule depolymerization.
Are tubulin colchicine pocket-ligand binding crystal structures suitable for preclinical applications?
Along with the rapid development of colchicine binding site inhibitors in the last decade, especially with the elucidations of several tubulin colchicine pocket-ligand binding crystal structures, more structures of CBSIs were reported and many of them showed excellent potency and drug-like properties for their preclinical applications.