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.

2.50
Hdl Handle:
http://hdl.handle.net/10033/618033
Title:
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.
Authors:
Ranade, Adwait R; Higgins, LeeAnn; Markowski, Todd W; Glaser, Nicole; Kashin, Dmitry; Bai, Ruoli; Hong, Kwon Ho; Hamel, Ernest; Höfle, Gerhard; Georg, Gunda I ( 0000-0002-8900-9460 )
Abstract:
Photoaffinity 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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
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. 2016, 59 (7):3499-514 J. Med. Chem.
Journal:
Journal of medicinal chemistry
Issue Date:
14-Apr-2016
URI:
http://hdl.handle.net/10033/618033
DOI:
10.1021/acs.jmedchem.6b00188
PubMed ID:
26986898
Type:
Article
Language:
en
ISSN:
1520-4804
Appears in Collections:
Publications of Scientific Director (GFW)

Full metadata record

DC FieldValue Language
dc.contributor.authorRanade, Adwait Ren
dc.contributor.authorHiggins, LeeAnnen
dc.contributor.authorMarkowski, Todd Wen
dc.contributor.authorGlaser, Nicoleen
dc.contributor.authorKashin, Dmitryen
dc.contributor.authorBai, Ruolien
dc.contributor.authorHong, Kwon Hoen
dc.contributor.authorHamel, Ernesten
dc.contributor.authorHöfle, Gerharden
dc.contributor.authorGeorg, Gunda Ien
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.en
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

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