Tubulin vinca-domain ligands can inhibit microtubule polymerization, causing cell death in mitosis, and their potential against multiple cancer types has been demonstrated. However, due to drug resistance toxicities, development of novel is still needed. In this study, we determined the high-resolution crystal structures vinorelbine, YXD, Phomopsin A complex with tubulin at 2.5 Å. Additionally,...

Background: Microtubules (MT) are important components of cell cytoskeleton and play key roles in cell motility mitosis and meiosis. They are also the targets of several anticancer agents which indicating their importance in maintaining cell viability. Microtubular reorganization contributing to apoptotic morphology occurs in normal and neoplastic cells undergoing apoptosis induced by cytotoxic...

The role of GTP hydrolysis in microtubule dynamics has been reinvestigated using an analogue of GTP, guanylyl-(alpha, beta)-methylene-diphosphonate (GMPCPP). This analogue binds to the tubulin exchangeable nucleotide binding site (E-site) with an affinity four to eightfold lower than GTP and promotes the polymerization of normal microtubules. The polymerization rate of microtubules with GMPCPP-...

Combretastatin A-4 (CA-4) is one of the most potent tubulin polymerization inhibitors. In this paper, the identification of some new CA-4 analogues as potential tubulin polymerization inhibitors is performed by combination of molecular modeling techniques including 3D-QSAR, molecular docking and molecular dynamics (MD) simulation. The built 3D-QSAR models show significant statistical quality an...

Incubation of 48,000 X g rat brain supernatants for 30 min at 37 degrees with 1-2 mM guanylyl 5'-methylenediphosphonate [Gmp(CH2)pp] results in polymerization of 95-98% of the tubulin present. This is considerably more than the 50% polymerization that can be achieved with the natural nucleotide, GTP, under optimal conditions. Gmp(CH2)pp is also much more effective than GTP in inducing polymeriz...

Tubulin-targeting molecules are widely used cancer therapeutic agents. They inhibit microtubule-based structures, including the mitotic spindle, ultimately preventing cell division. The final fates of microtubule-inhibited cells are however often heterogeneous and difficult to predict. While recent work has provided insight into the cell response to inhibitors of microtubule dynamics (taxanes),...

Clonal cells (N18) of the mouse neuroblastoma C-1300 can be induced to undergo a morphological differentiation characterized by the outgrowth of very long neurites (> 150 microns) that contain many microtubules. Because the marked increase in the number and length of microtubules is apparently not due to an increase in the concentration of tubulin subunits, the possible role of additional macro...

Tubulin was isolated from cultured cells of rose (Rosa, sp.cv. Paul's scarlet) by DEAE-Sephadex A50 chromatography, and the taxol-induced polymerization of microtubules in vitro was characterized at 24 degrees C by turbidity development, sedimentation analysis, and electron microscopy. Numerous, short microtubules were formed in the presence of taxol, and maximum levels of turbidity and polymer...