2c78
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Pulvomycin inhibits protein synthesis by preventing the formation of the | + | 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== | ==About this Structure== | ||
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[[Category: Thermus thermophilus]] | [[Category: Thermus thermophilus]] | ||
[[Category: dGTPase]] | [[Category: dGTPase]] | ||
| - | [[Category: Krab, I | + | [[Category: Krab, I M.]] |
| - | [[Category: Nielsen, R | + | [[Category: Nielsen, R C.]] |
[[Category: Nissen, P.]] | [[Category: Nissen, P.]] | ||
[[Category: Nyborg, J.]] | [[Category: Nyborg, J.]] | ||
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[[Category: translation elongation factor]] | [[Category: translation elongation factor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:45:38 2008'' |
Revision as of 14:45, 21 February 2008
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EF-TU COMPLEXED WITH A GTP ANALOG AND THE ANTIBIOTIC PULVOMYCIN
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
2C78 is a Single protein structure of sequence from Thermus thermophilus with , and as ligands. Active as dGTPase, with EC number 3.1.5.1 Known structural/functional Site: . 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 Thu Feb 21 16:45:38 2008
Categories: Single protein | Thermus thermophilus | DGTPase | Krab, I M. | Nielsen, R C. | Nissen, P. | Nyborg, J. | Okamura, S. | Parmeggiani, A. | GNP | MG | PUL | Antibiotic | Elongation factor | Gtp-binding | Gtpase | Hydrolase | Nucleotide-binding | Phosphorylation | Protein biosynthesis | Protein synthesis | Translation elongation factor
