Crystallographic characterization of the ribosomal binding site and molecular mechanism of action of Hygromycin A.

2.50
Hdl Handle:
http://hdl.handle.net/10757/608247
Title:
Crystallographic characterization of the ribosomal binding site and molecular mechanism of action of Hygromycin A.
Authors:
Kaminishi, Tatsuya; Schedlbauer, Andreas; Fabbretti, Attilio; Brandi, Letizia; Ochoa Lizarralde, Borja; He, Cheng-Guang; Milón, Pohl; Connell, Sean R; Gualerzi, Claudio O; Fucini, Paola
Citation:
Crystallographic characterization of the ribosomal binding site and molecular mechanism of action of Hygromycin A. 2015, 43 (20):10015-25 Nucleic Acids Res.
Publisher:
Oxford University Press
Journal:
Nucleic acids research (Nucleic Acids Res.)
Issue Date:
16-Nov-2015
URI:
http://hdl.handle.net/10757/608247
DOI:
10.1093/nar/gkv975
PubMed ID:
26464437
Additional Links:
http://nar.oxfordjournals.org/content/43/20/10015.long
Abstract:
Hygromycin A (HygA) binds to the large ribosomal subunit and inhibits its peptidyl transferase (PT) activity. The presented structural and biochemical data indicate that HygA does not interfere with the initial binding of aminoacyl-tRNA to the A site, but prevents its subsequent adjustment such that it fails to act as a substrate in the PT reaction. Structurally we demonstrate that HygA binds within the peptidyl transferase center (PTC) and induces a unique conformation. Specifically in its ribosomal binding site HygA would overlap and clash with aminoacyl-A76 ribose moiety and, therefore, its primary mode of action involves sterically restricting access of the incoming aminoacyl-tRNA to the PTC.
Type:
info:eu-repo/semantics/article
Rights:
info:eu-repo/semantics/openAccess
Language:
eng
Keywords:
Binding Sites; Cinnamates; X-Ray Crystallography; Hygromycin B; Models Molecular; Peptidyl Transferases; Ribosome Subunits; RNA
MeSH:
Binding Sites; Cinnamates; Crystallography, X-Ray; Hygromycin B; Models, Molecular; Peptidyl Transferases; Protein Synthesis Inhibitors; RNA, Transfer, Amino Acyl; Ribosome Subunits, Large, Bacterial
ISSN:
1362-4962
Sponsors:
Bizkaia:Talent and the European Union's Seventh Framework Program (Marie Curie Actions; COFUND; to S.C., A.S., T.K.); Marie Curie Actions Career Integration Grant (PCIG14-GA-2013-632072 to P.F.); Ministerio de Economía Y Competitividad (CTQ2014-55907-R to P.F., S.C.); FIRB Futuro in Ricerca from the Italian Ministero dell'Istruzione, dell'Universitá e della Ricerca (RBFR130VS5_001 to A.F.); Peruvian Programa Nacional de Innovación para la Competitividad y Productividad (382-PNICP-PIBA-2014 (to P.M. and A.F.)). Funding for open access charge: Institutional funding.
Email:
pfucini@gmail.com

Full metadata record

DC FieldValue Language
dc.contributor.authorKaminishi, Tatsuyaes_PE
dc.contributor.authorSchedlbauer, Andreases_PE
dc.contributor.authorFabbretti, Attilioes_PE
dc.contributor.authorBrandi, Letiziaes_PE
dc.contributor.authorOchoa Lizarralde, Borjaes_PE
dc.contributor.authorHe, Cheng-Guanges_PE
dc.contributor.authorMilón, Pohles_PE
dc.contributor.authorConnell, Sean Res_PE
dc.contributor.authorGualerzi, Claudio Oes_PE
dc.contributor.authorFucini, Paolaes_PE
dc.date.accessioned2016-05-04T16:10:06Zes_PE
dc.date.available2016-05-04T16:10:06Zes_PE
dc.date.issued2015-11-16es_PE
dc.identifier.citationCrystallographic characterization of the ribosomal binding site and molecular mechanism of action of Hygromycin A. 2015, 43 (20):10015-25 Nucleic Acids Res.es_PE
dc.identifier.issn1362-4962es_PE
dc.identifier.pmid26464437es_PE
dc.identifier.doi10.1093/nar/gkv975es_PE
dc.identifier.urihttp://hdl.handle.net/10757/608247es_PE
dc.description.abstractHygromycin A (HygA) binds to the large ribosomal subunit and inhibits its peptidyl transferase (PT) activity. The presented structural and biochemical data indicate that HygA does not interfere with the initial binding of aminoacyl-tRNA to the A site, but prevents its subsequent adjustment such that it fails to act as a substrate in the PT reaction. Structurally we demonstrate that HygA binds within the peptidyl transferase center (PTC) and induces a unique conformation. Specifically in its ribosomal binding site HygA would overlap and clash with aminoacyl-A76 ribose moiety and, therefore, its primary mode of action involves sterically restricting access of the incoming aminoacyl-tRNA to the PTC.es_PE
dc.description.sponsorshipBizkaia:Talent and the European Union's Seventh Framework Program (Marie Curie Actions; COFUND; to S.C., A.S., T.K.); Marie Curie Actions Career Integration Grant (PCIG14-GA-2013-632072 to P.F.); Ministerio de Economía Y Competitividad (CTQ2014-55907-R to P.F., S.C.); FIRB Futuro in Ricerca from the Italian Ministero dell'Istruzione, dell'Universitá e della Ricerca (RBFR130VS5_001 to A.F.); Peruvian Programa Nacional de Innovación para la Competitividad y Productividad (382-PNICP-PIBA-2014 (to P.M. and A.F.)). Funding for open access charge: Institutional funding.es_PE
dc.formatapplication/pdfes_PE
dc.language.isoenges_PE
dc.publisherOxford University Presses_PE
dc.relation.urlhttp://nar.oxfordjournals.org/content/43/20/10015.longes_PE
dc.rightsinfo:eu-repo/semantics/openAccesses_PE
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.sourceUniversidad Peruana de Ciencias Aplicadas (UPC)es_PE
dc.sourceRepositorio Académico - UPCes_PE
dc.subjectBinding Siteses_PE
dc.subjectCinnamateses_PE
dc.subjectX-Ray Crystallographyes_PE
dc.subjectHygromycin Bes_PE
dc.subjectModels Moleculares_PE
dc.subjectPeptidyl Transferaseses_PE
dc.subjectRibosome Subunitses_PE
dc.subjectRNAes_PE
dc.subject.meshBinding Siteses_PE
dc.subject.meshCinnamateses_PE
dc.subject.meshCrystallography, X-Rayes_PE
dc.subject.meshHygromycin Bes_PE
dc.subject.meshModels, Moleculares_PE
dc.subject.meshPeptidyl Transferaseses_PE
dc.subject.meshProtein Synthesis Inhibitorses_PE
dc.subject.meshRNA, Transfer, Amino Acyles_PE
dc.subject.meshRibosome Subunits, Large, Bacteriales_PE
dc.titleCrystallographic characterization of the ribosomal binding site and molecular mechanism of action of Hygromycin A.es_PE
dc.typeinfo:eu-repo/semantics/articlees_PE
dc.identifier.journalNucleic acids research (Nucleic Acids Res.)es_PE
dc.description.peer-reviewRevisión por pareses_PE
dc.contributor.emailpfucini@gmail.comes_PE
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