4UJZ: Crystal Structure Of Anisomycin Bound To The Yeast 80s Ribosome

Citation:
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.
MMDB ID: 124241
PDB Deposition Date: 2014/7/22
Updated in MMDB: 2014/11
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
Similar Structures:
Merged PDB IDs:4UJZ 4UK0 4UK1 4UK2 4UK3
Asymmetric Unit for 4UJZ: 162-meric
Molecular Components in 4UJZ
Label Count Molecule
Proteins (154 molecules)
2
40S Ribosomal Protein S0-a
Molecule annotation
2
40S Ribosomal Protein S1-a
Molecule annotation
2
40S Ribosomal Protein S2
Molecule annotation
2
40S Ribosomal Protein S3
Molecule annotation
2
40S Ribosomal Protein S4-a
Molecule annotation
2
40S Ribosomal Protein S5
Molecule annotation
2
40S Ribosomal Protein S6-a
Molecule annotation
2
40S Ribosomal Protein S7-a
Molecule annotation
2
40S Ribosomal Protein S8-a
Molecule annotation
2
40S Ribosomal Protein S9-a
Molecule annotation
2
40S Ribosomal Protein S10-b
Molecule annotation
2
40S Ribosomal Protein S11-a
Molecule annotation
2
40S Ribosomal Protein S12
Molecule annotation
2
40S Ribosomal Protein S13
Molecule annotation
2
40S Ribosomal Protein S14-a
Molecule annotation
2
40S Ribosomal Protein S15
Molecule annotation
2
40S Ribosomal Protein S16-a
Molecule annotation
2
40S Ribosomal Protein S17-a
Molecule annotation
2
40S Ribosomal Protein S18-a
Molecule annotation
2
40S Ribosomal Protein S19-a
Molecule annotation
2
40S Ribosomal Protein S20
Molecule annotation
2
40S Ribosomal Protein S21-a
Molecule annotation
2
40S Ribosomal Protein S22-a
Molecule annotation
2
40S Ribosomal Protein S23-a
Molecule annotation
2
40S Ribosomal Protein S24-a
Molecule annotation
2
40S Ribosomal Protein S25-a
Molecule annotation
2
40S Ribosomal Protein S26-b
Molecule annotation
2
40S Ribosomal Protein S27-a
Molecule annotation
2
40S Ribosomal Protein S28-a
Molecule annotation
2
40S Ribosomal Protein S29-a
Molecule annotation
1
40S Ribosomal Protein S30-a
Molecule annotation
1
Ubiquitin-40s Ribosomal Protein S31
Molecule annotation
2
Guanine Nucleotide-binding Protein Subunit Beta-like Protein
Molecule annotation
2
Suppressor Protein Stm1
Molecule annotation
2
60S Ribosomal Protein L2-a
Molecule annotation
2
60S Ribosomal Protein L3
Molecule annotation
2
60S Ribosomal Protein L4-a
Molecule annotation
2
60S Ribosomal Protein L5
Molecule annotation
2
60S Ribosomal Protein L6-a
Molecule annotation
2
60S Ribosomal Protein L7-a
Molecule annotation
2
60S Ribosomal Protein L8-a
Molecule annotation
2
60S Ribosomal Protein L9-a
Molecule annotation
2
60S Ribosomal Protein L10
Molecule annotation
2
60S Ribosomal Protein L11-b
Molecule annotation
2
60S Ribosomal Protein L13-a
Molecule annotation
2
60S Ribosomal Protein L14-a
Molecule annotation
2
60S Ribosomal Protein L15-a
Molecule annotation
2
60S Ribosomal Protein L16-a
Molecule annotation
2
60S Ribosomal Protein L17-a
Molecule annotation
2
60S Ribosomal Protein L18-a
Molecule annotation
2
60S Ribosomal Protein L19-a
Molecule annotation
2
60S Ribosomal Protein L20-a
Molecule annotation
2
60S Ribosomal Protein L21-a
Molecule annotation
2
60S Ribosomal Protein L22-a
Molecule annotation
2
60S Ribosomal Protein L23-a
Molecule annotation
2
60S Ribosomal Protein L24-a
Molecule annotation
2
60S Ribosomal Protein L25
Molecule annotation
2
60S Ribosomal Protein L26-a
Molecule annotation
2
60S Ribosomal Protein L27-a
Molecule annotation
2
60S Ribosomal Protein L28
Molecule annotation
2
60S Ribosomal Protein L29
Molecule annotation
2
60S Ribosomal Protein L30
Molecule annotation
2
60S Ribosomal Protein L31-a
Molecule annotation
2
60S Ribosomal Protein L32
Molecule annotation
2
60S Ribosomal Protein L33-a
Molecule annotation
2
60S Ribosomal Protein L34-a
Molecule annotation
2
60S Ribosomal Protein L35-a
Molecule annotation
2
60S Ribosomal Protein L36-a
Molecule annotation
2
60S Ribosomal Protein L37-a
Molecule annotation
2
60S Ribosomal Protein L38
Molecule annotation
2
60S Ribosomal Protein L39
Molecule annotation
2
Ubiquitin-60s Ribosomal Protein L40
Molecule annotation
2
60S Ribosomal Protein L41-a
Molecule annotation
2
60S Ribosomal Protein L42-a
Molecule annotation
2
60S Ribosomal Protein L43-a
Molecule annotation
1
40S Ribosomal Protein S30-a
Molecule annotation
1
Ubiquitin-40s Ribosomal Protein S31
Molecule annotation
1
Unknown Protein M2
Molecule annotation
1
60S Acidic Ribosomal Protein P0
Molecule annotation
1
Unknown Protein P1
Molecule annotation
1
Unknown Protein P2
Molecule annotation
Nucleotides(4 molecules)
2
18S rRNA
Molecule annotation
2
25S rRNA
Molecule annotation
2
5.8s rRNA
Molecule annotation
2
5.8s rRNA
Molecule annotation
Chemicals (2561 molecules)
1
1410
2
1133
3
16
4
2
* Click molecule labels to explore molecular sequence information.

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