2c77
From Proteopedia
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[[Image:2c77.gif|left|200px]] | [[Image:2c77.gif|left|200px]] | ||
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'''EF-TU COMPLEXED WITH A GTP ANALOG AND THE ANTIBIOTIC GE2270 A''' | '''EF-TU COMPLEXED WITH A GTP ANALOG AND THE ANTIBIOTIC GE2270 A''' | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Thermus thermophilus]] | [[Category: Thermus thermophilus]] | ||
- | [[Category: | + | [[Category: DGTPase]] |
[[Category: Krab, I M.]] | [[Category: Krab, I M.]] | ||
[[Category: Nielsen, R C.]] | [[Category: Nielsen, R C.]] | ||
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[[Category: Okamura, S.]] | [[Category: Okamura, S.]] | ||
[[Category: Parmeggiani, A.]] | [[Category: Parmeggiani, A.]] | ||
- | [[Category: | + | [[Category: Antibiotic]] |
- | [[Category: | + | [[Category: Gtp-binding]] |
- | [[Category: | + | [[Category: Gtpase]] |
- | [[Category: | + | [[Category: Hydrolase]] |
- | [[Category: | + | [[Category: Nucleotide-binding]] |
- | [[Category: | + | [[Category: Phosphorylation]] |
- | [[Category: | + | [[Category: Protein biosynthesis]] |
- | [[Category: | + | [[Category: Protein synthesis]] |
- | [[Category: | + | [[Category: Translation elongation factor]] |
- | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 21:22:06 2008'' | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + |
Revision as of 18:22, 3 May 2008
EF-TU COMPLEXED WITH A GTP ANALOG AND THE ANTIBIOTIC GE2270 A
Overview
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.
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 Page seeded by OCA on Sat May 3 21:22:06 2008
Categories: Single protein | Thermus thermophilus | DGTPase | Krab, I M. | Nielsen, R C. | Nissen, P. | Nyborg, J. | Okamura, S. | Parmeggiani, A. | Antibiotic | Gtp-binding | Gtpase | Hydrolase | Nucleotide-binding | Phosphorylation | Protein biosynthesis | Protein synthesis | Translation elongation factor