PDBsum entry 4uke

Ribosome

PDB id: 4uke

Contents

Protein chains

213 a.a.

169 a.a.

150 a.a.

194 a.a.

137 a.a.

203 a.a.

197 a.a.

155 a.a.

185 a.a.

188 a.a.

172 a.a.

159 a.a.

98 a.a.

136 a.a.

135 a.a.

120 a.a.

126 a.a.

135 a.a.

148 a.a.

58 a.a.

100 a.a.

109 a.a.

127 a.a.

106 a.a.

112 a.a.

119 a.a.

99 a.a.

87 a.a.

77 a.a.

50 a.a.

52 a.a.

25 a.a.

105 a.a.

91 a.a.

143 a.a.

47 a.a.

Ligands

OHX ×15

Metals

_MG ×27

_ZN ×4

Obsolete entry

PDB id:

4uke

Name:

Ribosome

Title:

Crystal structure of cycloheximide bound to the yeast 80s ribosome

Structure:

60s ribosomal protein l10. Chain: a. Synonym: l9,ubiquinol-cytochromE C reductase complex subunit vi- requiring protein. 60s ribosomal protein l11-b. Chain: b. Synonym: l16,rp39,yl22. Unknown protein m2. Chain: c.

Source:

Saccharomyces cerevisiae atcc 204508 / s288c. Organism_taxid: 559292. Organism_taxid: 559292

Resolution:

2.90Å R-factor: 0.205 R-free: 0.245

Authors:

N.Garreau De Loubresse,I.Prokhorova,G.Yusupova,M.Yusupov

Key ref:

N.Garreau de Loubresse et al. (2014). Structural basis for the inhibition of the eukaryotic ribosome. Nature, 513, 517-522. PubMed id: 25209664 DOI: 10.1038/nature13737

Date:

22-Jul-14 Release date: 22-Oct-14

Protein chain

P41805  (RL10_YEAST) -  60S ribosomal protein L10 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 221 a.a.

Struc: 213 a.a.

Protein chain

Q3E757  (RL11B_YEAST) -  60S ribosomal protein L11-B from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 174 a.a.

Struc: 169 a.a.

Protein chain

No UniProt id for this chain

Struc: 150 a.a.

Protein chain

Q12690  (RL13A_YEAST) -  60S ribosomal protein L13-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 199 a.a.

Struc: 194 a.a.

Protein chain

P36105  (RL14A_YEAST) -  60S ribosomal protein L14-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 138 a.a.

Struc: 137 a.a.

Protein chain

P05748  (RL15A_YEAST) -  60S ribosomal protein L15-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 204 a.a.

Struc: 203 a.a.

Protein chain

P26784  (RL16A_YEAST) -  60S ribosomal protein L16-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 199 a.a.

Struc: 197 a.a.

Protein chain

P05740  (RL17A_YEAST) -  60S ribosomal protein L17-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 184 a.a.

Struc: 155 a.a.

Protein chain

P0CX49  (RL18A_YEAST) -  60S ribosomal protein L18-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 186 a.a.

Struc: 185 a.a.

Protein chain

P0CX82  (RL19A_YEAST) -  60S ribosomal protein L19-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 189 a.a.

Struc: 188 a.a.

Protein chain

P0CX23  (RL20A_YEAST) -  60S ribosomal protein L20-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 172 a.a.

Struc: 172 a.a.

Protein chain

Q02753  (RL21A_YEAST) -  60S ribosomal protein L21-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 160 a.a.

Struc: 159 a.a.

Protein chain

P05749  (RL22A_YEAST) -  60S ribosomal protein L22-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 121 a.a.

Struc: 98 a.a.

Protein chain

P0CX41  (RL23A_YEAST) -  60S ribosomal protein L23-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 137 a.a.

Struc: 136 a.a.

Protein chain

P04449  (RL24A_YEAST) -  60S ribosomal protein L24-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 155 a.a.

Struc: 135 a.a.

Protein chain

P04456  (RL25_YEAST) -  60S ribosomal protein L25 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 142 a.a.

Struc: 120 a.a.

Protein chain

P05743  (RL26A_YEAST) -  60S ribosomal protein L26-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 127 a.a.

Struc: 126 a.a.

Protein chain

P0C2H6  (RL27A_YEAST) -  60S ribosomal protein L27-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 136 a.a.

Struc: 135 a.a.

Protein chain

P02406  (RL28_YEAST) -  60S ribosomal protein L28 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 149 a.a.

Struc: 148 a.a.

Protein chain

P05747  (RL29_YEAST) -  60S ribosomal protein L29 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 59 a.a.

Struc: 58 a.a.

Protein chain

P14120  (RL30_YEAST) -  60S ribosomal protein L30 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 105 a.a.

Struc: 100 a.a.

Protein chain

P0C2H8  (RL31A_YEAST) -  60S ribosomal protein L31-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 113 a.a.

Struc: 109 a.a.

Protein chain

P38061  (RL32_YEAST) -  60S ribosomal protein L32 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 130 a.a.

Struc: 127 a.a.

Protein chain

P05744  (RL33A_YEAST) -  60S ribosomal protein L33-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 107 a.a.

Struc: 106 a.a.

Protein chain

P87262  (RL34A_YEAST) -  60S ribosomal protein L34-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 121 a.a.

Struc: 112 a.a.

Protein chain

P0CX84  (RL35A_YEAST) -  60S ribosomal protein L35-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 120 a.a.

Struc: 119 a.a.

Protein chain

P05745  (RL36A_YEAST) -  60S ribosomal protein L36-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 100 a.a.

Struc: 99 a.a.

Protein chain

P49166  (RL37A_YEAST) -  60S ribosomal protein L37-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 88 a.a.

Struc: 87 a.a.

Protein chain

P49167  (RL38_YEAST) -  60S ribosomal protein L38 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 78 a.a.

Struc: 77 a.a.

Protein chain

P04650  (RL39_YEAST) -  60S ribosomal protein L39 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 51 a.a.

Struc: 50 a.a.

Protein chain

P0CH08  (RL40A_YEAST) -  Ubiquitin-60S ribosomal protein L40 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 128 a.a.

Struc: 52 a.a.

Protein chain

P0CX86  (RL41A_YEAST) -  60S ribosomal protein L41-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 25 a.a.

Struc: 25 a.a.

Protein chain

P0CX27  (RL44A_YEAST) -  60S ribosomal protein L42-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 106 a.a.

Struc: 105 a.a.

Protein chain

P0CX25  (RL43A_YEAST) -  60S ribosomal protein L43-A from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 92 a.a.

Struc: 91 a.a.

Protein chain

P05317  (RLA0_YEAST) -  60S acidic ribosomal protein P0 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 312 a.a.

Struc: 143 a.a.

Protein chains

No UniProt id for this chain

Struc: 47 a.a.

DOI no: 10.1038/nature13737

Nature 513:517-522 (2014)

PubMed id: 25209664

Structural basis for the inhibition of the eukaryotic ribosome.

N.Garreau de Loubresse, I.Prokhorova, W.Holtkamp, M.V.Rodnina, G.Yusupova, M.Yusupov.

ABSTRACT

The ribosome is a molecular machine responsible for protein synthesis and a major target for small-molecule inhibitors. Compared to the wealth of structural information available on ribosome-targeting antibiotics in bacteria, our understanding of the binding mode of ribosome inhibitors in eukaryotes is currently limited. Here we used X-ray crystallography to determine 16 high-resolution structures of 80S ribosomes from Saccharomyces cerevisiae in complexes with 12 eukaryote-specific and 4 broad-spectrum inhibitors. All inhibitors were found associated with messenger RNA and transfer RNA binding sites. In combination with kinetic experiments, the structures suggest a model for the action of cycloheximide and lactimidomycin, which explains why lactimidomycin, the larger compound, specifically targets the first elongation cycle. The study defines common principles of targeting and resistance, provides insights into translation inhibitor mode of action and reveals the structural determinants responsible for species selectivity which could guide future drug development.