1OB5

T. aquaticus elongation factor EF-Tu complexed with the antibiotic enacyloxin IIa, a GTP analog, and Phe-tRNA

Summary for 1OB5

• Entry DOI: 10.2210/pdb1ob5/pdb
• Related: 1B23 1EFT 1H1U 1IPM 1IPO 1IPQ 1IPR 1IPU 1L1U 1TTT 1TUI
• Descriptor: ELONGATION FACTOR TU, TRANSFER-RNA, PHE, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (5 entities in total)
• Functional Keywords: hydrolase, gtpase, translation elongation factor, transfer rna, gtp-binding, nucleotide-binding, protein biosynthesis
• Biological source: THERMUS AQUATICUS; More
• Total number of polymer chains: 6
• Total formula weight: 213955.73

Authors

Dahlberg, C.,Nielsen, R.C.,Parmeggiani, A.,Nyborg, J.,Nissen, P. (deposition date: 2003-01-24, release date: 2005-10-13, Last modification date: 2023-12-13)

Primary citation

Parmeggiani, A.,Krab, I.M.,Watanabe, T.,Nielsen, R.C.,Dahlberg, C.,Nyborg, J.,Nissen, P.
Enacyloxin Iia Pinpoints a Binding Pocket of Elongation Factor TU for Development of Novel Antibiotics.
J.Biol.Chem., 281:2893-, 2006

PubMed Abstract: Elongation factor (EF-) Tu.GTP is the carrier of aminoacyl-tRNA to the programmed ribosome. Enacyloxin IIa inhibits bacterial protein synthesis by hindering the release of EF-Tu.GDP from the ribosome. The crystal structure of the Escherichia coli EF-Tu.guanylyl iminodiphosphate (GDPNP).enacyloxin IIa complex at 2.3 A resolution presented here reveals the location of the antibiotic at the interface of domains 1 and 3. The binding site overlaps that of kirromycin, an antibiotic with a structure that is unrelated to enacyloxin IIa but that also inhibits EF-Tu.GDP release. As one of the major differences, the enacyloxin IIa tail borders a hydrophobic pocket that is occupied by the longer tail of kirromycin, explaining the higher binding affinity of the latter. EF-Tu.GDPNP.enacyloxin IIa shows a disordered effector region that in the Phe-tRNAPhe.EF-Tu (Thermus aquaticus).GDPNP.enacyloxin IIa complex, solved at 3.1 A resolution, is stabilized by the interaction with tRNA. This work clarifies the structural background of the action of enacyloxin IIa and compares its properties with those of kirromycin, opening new perspectives for structure-guided design of novel antibiotics.

PubMed: 16257965
DOI: 10.1074/JBC.M505951200

Experimental method

X-RAY DIFFRACTION (3.1 Å)