PDBsum entry 2npf

Translation

PDB id: 2npf

Contents

Protein chains

822 a.a. *

Ligands

MOU ×2

GDP ×2

* Residue conservation analysis

PDB id:

2npf

Name:

Translation

Title:

Structure of eef2 in complex with moriniafungin

Structure:

Elongation factor 2. Chain: a, b. Synonym: ef-2, translation elongation factor 2, eukaryotic elongation factor 2, eef2, ribosomal translocase

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932

Resolution:

2.90Å R-factor: 0.230 R-free: 0.271

Authors:

R.Soe,R.T.Mosley,G.R.Andersen

Key ref:

R.Søe et al. (2007). Sordarin derivatives induce a novel conformation of the yeast ribosome translocation factor eEF2. J Biol Chem, 282, 657-666. PubMed id: 17082187 DOI: 10.1074/jbc.M607830200

Date:

27-Oct-06 Release date: 14-Nov-06

Protein chains

P32324  (EF2_YEAST) -  Elongation factor 2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 842 a.a.

Struc: 822 a.a.

DOI no: 10.1074/jbc.M607830200

J Biol Chem 282:657-666 (2007)

PubMed id: 17082187

Sordarin derivatives induce a novel conformation of the yeast ribosome translocation factor eEF2.

R.Søe, R.T.Mosley, M.Justice, J.Nielsen-Kahn, M.Shastry, A.R.Merrill, G.R.Andersen.

ABSTRACT

The sordarins are fungal specific inhibitors of the translation factor eEF2, which catalyzes the translocation of tRNA and mRNA after peptide bond formation. We have determined the crystal structures of eEF2 in complex with two novel sordarin derivatives. In both structures, the three domains of eEF2 that form the ligand-binding pocket are oriented in a different manner relative to the rest of eEF2 compared with our previous structure of eEF2 in complex with the parent natural product sordarin. Yeast eEF2 is also shown to bind adenylic nucleotides, which can be displaced by sordarin, suggesting that ADP or ATP also bind to the three C-terminal domains of eEF2. Fusidic acid is a universal inhibitor of translation that targets EF-G or eEF2 and is widely used as an antibiotic against Gram-positive bacteria. Based on mutations conferring resistance to fusidic acid, cryo-EM reconstructions, and x-ray structures of eEF2, EF-G, and an EF-G homolog, we suggest that the conformation of EF-G stalled on the 70 S ribosome by fusidic acid is similar to that of eEF2 trapped on the 80 S ribosome by sordarin.

Selected figure(s)

Figure 1.
FIGURE 1. The chemical structures of the natural products sordarin and moriniafungin, as well as the semisynthetic analog compound 1.

Figure 6.
FIGURE 6. A conserved conformation of eEF2 and EF-G. A, fusidic acid related mutations mapped on the crystal structure of EF-G (Protein Data Bank entry 1FNM). The backbone of 30 fusidic acid resistance residues (41) is colored blue. B, mapping onto an EF-G model derived from the conformation of eEF2 observed by cryo-EM (see text for details). The closer approach of domain III to domain I in this model is illustrated by the distances between Leu^457 and Gln^117 (dashed lines). The distance is 16.5 Å in the crystal structure and 12.1 Å in the modeled structure. C, overlay of domains III (blue), IV (red), and V (green) of eEF2-sordarin and the equivalent domains of the T. thermophilus EF-G homolog (all domains gray) from Protein Data Bank entry 1WDT illustrating a highly conserved domain arrangement.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 657-666) copyright 2007.

Figures were selected by an automated process.