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2c78
From Proteopedia
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| , resolution 1.4Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , | ||||||
| Activity: | dGTPase, with EC number 3.1.5.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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 Mon Mar 31 02:17:21 2008
Categories: Single protein | Thermus thermophilus | DGTPase | Krab, I M. | Nielsen, R C. | Nissen, P. | Nyborg, J. | Okamura, S. | Parmeggiani, A. | Antibiotic | Elongation factor | Gtp-binding | Gtpase | Hydrolase | Nucleotide-binding | Phosphorylation | Protein biosynthesis | Protein synthesis | Translation elongation factor
