Characterizing the Epothilone Binding Site on β-Tubulin by Photoaffinity Labeling: Identification of β-Tubulin Peptides TARGSQQY and TSRGSQQY as Targets of an Epothilone Photoprobe for Polymerized Tubulin
نویسندگان
چکیده
منابع مشابه
Computational study of binding of epothilone A to β-tubulin.
Understanding the interactions of epothilones with β-tubulin is crucial for computer aided rational design of macrocyclic drugs based on epothilones and epothilone derivatives. Despite numerous structure-activity relationship investigations we still lack substantial knowledge about the binding mode of epothilones and their derivatives to β-tubulin. In this work, we reevaluated the electron crys...
متن کاملThe Binding Mode of Epothilone A on , -Tubulin by Electron Crystallography
The structure of epothilone A, bound to , -tubulin in zinc-stabilized sheets, was determined by a combination of electron crystallography at 2.89 angstrom resolution and nuclear magnetic resonance–based conformational analysis. The complex explains both the broad-based epothilone structureactivity relationship and the known mutational resistance profile. Comparison with Taxol shows that the lon...
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Ultraviolet irradiation of the [3H]colchicine-tubulin complex leads to direct photolabeling of tubulin with low but practicable efficiency. The bulk (70% to greater than 90%) of the labeling occurs on beta-tubulin and appears early after irradiation, whereas alpha-tubulin is labeled later. The labeling ratio of beta-tubulin to alpha-tubulin (beta/alpha ratio) is reduced by prolonged incubation,...
متن کاملcomparison of epothilone and taxol binding in yeast tubulin using molecular modeling
microtubules are unique cytoskeletal structures that have structural subunits of αβ tubulin. taxol is a typical microtubule stabilizing drug. the epothilones are other natural products with similar mechanism of action totaxol. despite the highly conserved nature of β-tubulin, some organism like saccharomyces cerevesia is resistance to taxol, but sensitive to epothilones. in order to find differ...
متن کاملMolecular Modeling Studies on Vinblastine Binding Site of Tubulin for Antimitotic agents
Medicinal chemistry depends on many other disciplines ranging from organic chemistry andpharmacology to computational chemistry. Typically medicinal chemists use the moststraightforward ways to prepare compounds. The validation of any design project comes from thebiological testing.Studies of the binding site of vinblastine by a single cross—linking experiment identified it asbeing between resi...
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ژورنال
عنوان ژورنال: Journal of Medicinal Chemistry
سال: 2016
ISSN: 0022-2623,1520-4804
DOI: 10.1021/acs.jmedchem.6b00188