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

Description

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. / 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. / Revisión por pares

Links & Downloads

1. Crystallographic characterization of the ribosomal binding site and molecular mechanism of action of Hygromycin A. 2015, 43 (20):10015-25 Nucleic Acids Res.
2. 1362-4962
3. 26464437
4. 10.1093/nar/gkv975
5. http://hdl.handle.net/10757/608247
6. Nucleic acids research (Nucleic Acids Res.)

Tags

Binding Sites

Cinnamates

X-Ray Crystallography

Hygromycin B

Models Molecular

Peptidyl Transferases

Ribosome Subunits

RNA

Binding Sites

Cinnamates

Crystallography, X-Ray

Hygromycin B

Models, Molecular

Peptidyl Transferases

Protein Synthesis Inhibitors

RNA, Transfer, Amino Acyl

Ribosome Subunits, Large, Bacterial

Additional Fields

Identifer	oai:union.ndltd.org:PERUUPC/oai:repositorioacademico.upc.edu.pe:10757/608247
Date	16 November 2015
Creators	Kaminishi, Tatsuya, Schedlbauer, Andreas, Fabbretti, Attilio, Brandi, Letizia, Ochoa Lizarralde, Borja, He, Cheng-Guang, Milon, Pohl, Connell, Sean R, Gualerzi, Claudio O, Fucini, Paola
Contributors	[e-mail]
Publisher	Oxford University Press
Source Sets	Universidad Peruana de Ciencias Aplicadas (UPC)
Language	English
Detected Language	English
Type	info:eu-repo/semantics/article
Format	application/pdf
Source	Universidad Peruana de Ciencias Aplicadas (UPC), Repositorio Académico - UPC
Rights	info:eu-repo/semantics/openAccess, http://creativecommons.org/licenses/by-nc-nd/4.0/
Relation	http://nar.oxfordjournals.org/content/43/20/10015.long