2C78

EF-Tu complexed with a GTP analog and the antibiotic pulvomycin

Summary for 2C78

• Entry DOI: 10.2210/pdb2c78/pdb
• Related: 1HA3
• Descriptor: ELONGATION FACTOR TU-A, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: hydrolase, gtpase, translation elongation factor, protein synthesis, antibiotic, gtp-binding, nucleotide-binding, phosphorylation, protein biosynthesis, elongation factor
• Biological source: THERMUS THERMOPHILUS
• Total number of polymer chains: 1
• Total formula weight: 46067.36

Authors

Parmeggiani, A.,Krab, I.M.,Okamura, S.,Nielsen, R.C.,Nyborg, J.,Nissen, P. (deposition date: 2005-11-18, release date: 2006-03-16, Last modification date: 2023-12-13)

Primary citation

Parmeggiani, A.,Krab, I.M.,Okamura, S.,Nielsen, R.C.,Nyborg, J.,Nissen, P.
Structural basis of the action of pulvomycin and GE2270 A on elongation factor Tu.
Biochemistry, 45:6846-6857, 2006

PubMed Abstract: 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.

PubMed: 16734421
DOI: 10.1021/bi0525122

Experimental method

X-RAY DIFFRACTION (1.4 Å)