2c77

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{{STRUCTURE_2c77| PDB=2c77 | SCENE= }}
{{STRUCTURE_2c77| PDB=2c77 | SCENE= }}
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'''EF-TU COMPLEXED WITH A GTP ANALOG AND THE ANTIBIOTIC GE2270 A'''
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===EF-TU COMPLEXED WITH A GTP ANALOG AND THE ANTIBIOTIC GE2270 A===
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==Overview==
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Pulvomycin inhibits protein synthesis by preventing the formation of the ternary complex between elongation factor Tu (EF-Tu) x GTP and aa-tRNA. In this work, the crystal structure of Thermus thermophilus EF-Tu x pulvomycin in complex with the GTP analogue guanylyl imino diphosphate (GDPNP) at 1.4 A resolution reveals an antibiotic binding site extending from the domain 1-3 interface to domain 2, overlapping the domain 1-2-3 junction. Pulvomycin binding interferes with the binding of the 3'-aminoacyl group, the acceptor stem, and 5' end of tRNA. Only part of pulvomycin overlaps the binding site of GE2270 A, a domain 2-bound antibiotic of a structure unrelated to pulvomycin, which also hinders aa-tRNA binding. The structure of the T. thermophilus EF-Tu x GDPNP x GE2270 A complex at 1.6 A resolution shows that GE2270 A interferes with the binding of the 3'-aminoacyl group and part of the acceptor stem of aa-tRNA but not with the 5' end. Both compounds, pulvomycin more markedly, hinder the correct positioning of domain 1 over domains 2 and 3 that characterizes the active form of EF-Tu, while they affect the domain 1 switch regions that control the EF-Tu x GDP/GTP transitions in different ways. This work reveals how two antibiotics with different structures and binding modes can employ a similar mechanism of action.
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(as it appears on PubMed at http://www.pubmed.gov), where 16734421 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16734421}}
==About this Structure==
==About this Structure==
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[[Category: Protein synthesis]]
[[Category: Protein synthesis]]
[[Category: Translation elongation factor]]
[[Category: Translation elongation factor]]
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Revision as of 20:33, 27 July 2008

Template:STRUCTURE 2c77

EF-TU COMPLEXED WITH A GTP ANALOG AND THE ANTIBIOTIC GE2270 A

Template:ABSTRACT PUBMED 16734421

About this Structure

2C77 is a Single protein structure of sequence from Thermus thermophilus. Full crystallographic information is available from OCA.

Reference

Structural basis of the action of pulvomycin and GE2270 A on elongation factor Tu., Parmeggiani A, Krab IM, Okamura S, Nielsen RC, Nyborg J, Nissen P, Biochemistry. 2006 Jun 6;45(22):6846-57. PMID:16734421

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