alexa Identification of 12Cysbeta on tubulin as the binding site of tubulyzine.
Chemistry

Chemistry

Medicinal Chemistry

Author(s): Kim YJ, Sackett DL, Schapira M, Walsh DP, Min J,

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Abstract We have undertaken quantitative binding site studies in order to identify the binding site of the known microtubule destabilizing agents, the tubulyzines, in the tubulin dimer. Two different approaches were employed that utilized the tubulyzines and their derivatives. The first approach was based on a chemical affinity labeling method using tubulyzine affinity derivatives, and the second approach employed the mass spectrometric measurement of the differential reactivity of cysteines using the tubulyzines and monobromobimane. Based on overlapping data from these two approaches, we propose that the tubulyzines bind at the guanosine-5'-triphosphate binding site of beta-tubulin. Interestingly, we also show that the tubulyzines' binding to tubulin induces a conformational change in tubulin that prevents further interaction of the 239Cysbeta with other reagents.
This article was published in Bioorg Med Chem and referenced in Medicinal Chemistry

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