PDBsum entry 3g4s

Ribosome

PDB id: 3g4s

Contents

Protein chains

237 a.a.

337 a.a.

246 a.a.

140 a.a.

172 a.a.

119 a.a.

29 a.a.

160 a.a.

70 a.a.

142 a.a.

132 a.a.

145 a.a.

194 a.a.

186 a.a.

115 a.a.

143 a.a.

95 a.a.

150 a.a.

81 a.a.

119 a.a.

53 a.a.

65 a.a.

154 a.a.

82 a.a.

142 a.a.

73 a.a.

56 a.a.

46 a.a.

92 a.a.

DNA/RNA

Ligands

MUL

Metals

_SR ×108

_NA ×75

_MG ×93

_CL ×22

_CD ×5

__K

Waters ×7822

References listed in PDB file

Key reference

Title

U2504 determines the species specificity of the a-Site cleft antibiotics: the structures of tiamulin, Homoharringtonine, And bruceantin bound to the ribosome.

Authors

G.Gürel, G.Blaha, P.B.Moore, T.A.Steitz.

Ref.

J Mol Biol, 2009, 389, 146-156. [DOI no: 10.1016/j.jmb.2009.04.005]

PubMed id

19362093

Abstract

Structures have been obtained for the complexes that tiamulin, homoharringtonine, and bruceantin form with the large ribosomal subunit of Haloarcula marismortui at resolutions ranging from 2.65 to 3.2 A. They show that all these inhibitors block protein synthesis by competing with the amino acid side chains of incoming aminoacyl-tRNAs for binding in the A-site cleft in the peptidyl-transferase center, which is universally conserved. In addition, these structures support the hypothesis that the species specificity exhibited by the A-site cleft inhibitors is determined by the interactions they make, or fail to make, with a single nucleotide, U2504 (Escherichia coli). In the ribosome, the position of U2504 is controlled by its interactions with neighboring nucleotides, whose identities vary among kingdoms.

Figure 2.
Fig. 2. The chemical structures of tiamulin, homoharringtonine, and bruceantin and the corresponding difference electron density. Panels (a)–(c) show the chemical structures of these inhibitors. Panels (d)–(f) show the feature in the appropriate (F[o] − F[o]) difference electron density map that was assigned to the three drugs, with the structures of the drugs superimposed on them. Difference electron density maps were contoured at 3σ. Residues forming the A-site cleft are shown in cyan, and 23S rRNA bases are numbered to correspond with the 23S rRNA of E. coli.

Figure 6.
Fig. 6. Choosing the correct homoharringtonine enantiomer. A stereo pair that compares the fit of the refined homoharringtonine structure (gold) to the electron density for that drug with the fit obtained for the homoharringtonine structure obtained from the CSD (green), which is its enantiomer, is provided. The electron density shown is F[o] − F[o] difference electron density contoured at 3σ.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2009, 389, 146-156) copyright 2009.