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dc.contributor.authorRanade, Adwait R
dc.contributor.authorHiggins, LeeAnn
dc.contributor.authorMarkowski, Todd W
dc.contributor.authorGlaser, Nicole
dc.contributor.authorKashin, Dmitry
dc.contributor.authorBai, Ruoli
dc.contributor.authorHong, Kwon Ho
dc.contributor.authorHamel, Ernest
dc.contributor.authorHöfle, Gerhard
dc.contributor.authorGeorg, Gunda I
dc.date.accessioned2016-08-08T14:15:44Z
dc.date.available2016-08-08T14:15:44Z
dc.date.issued2016-04-14
dc.identifier.citationCharacterizing 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. 2016, 59 (7):3499-514 J. Med. Chem.en
dc.identifier.issn1520-4804
dc.identifier.pmid26986898
dc.identifier.doi10.1021/acs.jmedchem.6b00188
dc.identifier.urihttp://hdl.handle.net/10033/618033
dc.description.abstractPhotoaffinity labeling with an epothilone A photoprobe led to the identification of the β-tubulin peptides TARGSQQY and TSRGSQQY as targets of the photoprobe for polymerized tubulin. These peptides represent residues 274-281 in different β-tubulin isotypes. Placing the carbene producing 21-diazo/triazolo moiety of the photoprobe in the vicinity of the TARGSQQY peptide in a homology model of TBB3 predicted a binding pose and conformation of the photoprobe that are very similar to the ones reported for 1) the high resolution cocrystal structure of epothilone A with an α,β-tubulin complex and for 2) a saturation transfer difference NMR and transferred NOESY NMR study of dimeric and polymerized tubulin. Our findings thus provide additional support for these models as physiologically the most relevant among several modes of binding that have been proposed for epothilone A in the taxane pocket of β-tubulin.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/*
dc.titleCharacterizing 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.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalJournal of medicinal chemistryen
refterms.dateFOA2018-06-13T02:24:02Z
html.description.abstractPhotoaffinity labeling with an epothilone A photoprobe led to the identification of the β-tubulin peptides TARGSQQY and TSRGSQQY as targets of the photoprobe for polymerized tubulin. These peptides represent residues 274-281 in different β-tubulin isotypes. Placing the carbene producing 21-diazo/triazolo moiety of the photoprobe in the vicinity of the TARGSQQY peptide in a homology model of TBB3 predicted a binding pose and conformation of the photoprobe that are very similar to the ones reported for 1) the high resolution cocrystal structure of epothilone A with an α,β-tubulin complex and for 2) a saturation transfer difference NMR and transferred NOESY NMR study of dimeric and polymerized tubulin. Our findings thus provide additional support for these models as physiologically the most relevant among several modes of binding that have been proposed for epothilone A in the taxane pocket of β-tubulin.


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