4U4O

Crystal structure of Geneticin bound to the yeast 80S ribosome


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.60 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.191 

Starting Models: experimental
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wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Structural basis for the inhibition of the eukaryotic ribosome.

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

(2014) Nature 513: 517-522

  • DOI: https://doi.org/10.1038/nature13737
  • Primary Citation of Related Structures:  
    4U3M, 4U3N, 4U3U, 4U4N, 4U4O, 4U4Q, 4U4R, 4U4U, 4U4Y, 4U4Z, 4U50, 4U51, 4U52, 4U53, 4U55, 4U56, 4U6F

  • PubMed 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.


  • Organizational Affiliation

    Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR7104, Université de Strasbourg, 67404, Illkirch, France.


Macromolecules

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S0-AB [auth S0],
CC [auth s0]
251Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S1-AC [auth S1],
DC [auth s1]
254Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S2D [auth S2],
EC [auth s2]
253Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S3E [auth S3],
FC [auth s3]
239Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 6
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S4-AF [auth S4],
GC [auth s4]
260Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 7
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S5G [auth S5],
HC [auth s5]
224Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 8
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S6-AH [auth S6],
IC [auth s6]
236Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 9
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S7-AI [auth S7],
JC [auth s7]
189Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 10
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S8-AJ [auth S8],
KC [auth s8]
200Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 11
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S9-AK [auth S9],
LC [auth s9]
196Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 12
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S10-AL [auth C0],
MC [auth c0]
105Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 13
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S11-AM [auth C1],
NC [auth c1]
155Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 14
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S12N [auth C2],
OC [auth c2]
142Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 15
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S13O [auth C3],
PC [auth c3]
150Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 16
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S14-AP [auth C4],
QC [auth c4]
136Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 17
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S15Q [auth C5],
RC [auth c5]
141Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
Find proteins for Q01855 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c))
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Entity ID: 18
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S16-AR [auth C6],
SC [auth c6]
142Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
Find proteins for P0CX51 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c))
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Entity ID: 19
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S17-AS [auth C7],
TC [auth c7]
136Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 20
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S18-AT [auth C8],
UC [auth c8]
145Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
Find proteins for P0CX55 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c))
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Entity ID: 21
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S19-AU [auth C9],
VC [auth c9]
143Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 22
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S20V [auth D0],
WC [auth d0]
120Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 23
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S21-AW [auth D1],
XC [auth d1]
87Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 24
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S22-AX [auth D2],
YC [auth d2]
129Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 25
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S23-AY [auth D3],
ZC [auth d3]
144Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 26
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S24-AAD [auth d4],
Z [auth D4]
134Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 27
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S25-AAA [auth D5],
BD [auth d5]
107Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 28
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S26-BBA [auth D6],
CD [auth d6]
97Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 29
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S27-ACA [auth D7],
DD [auth d7]
81Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 30
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S28-ADA [auth D8],
ED [auth d8]
66Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
Find proteins for Q3E7X9 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c))
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Entity ID: 31
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S29-AEA [auth D9],
FD [auth d9]
55Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 32
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S30-AFA [auth E0]60Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 33
MoleculeChains Sequence LengthOrganismDetailsImage
Ubiquitin-40S ribosomal protein S31GA [auth E1]76Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 34
MoleculeChains Sequence LengthOrganismDetailsImage
Guanine nucleotide-binding protein subunit beta-like proteinHA [auth SR],
ID [auth sR]
318Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 35
MoleculeChains Sequence LengthOrganismDetailsImage
Suppressor protein STM1IA [auth SM],
JD [auth sM]
273Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 39
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L2-AMA [auth L2],
ND [auth l2]
253Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 40
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L3NA [auth L3],
OD [auth l3]
386Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 41
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L4-AOA [auth L4],
PD [auth l4]
361Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 42
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L5PA [auth L5],
QD [auth l5]
296Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 43
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L6-AQA [auth L6],
RD [auth l6]
175Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 44
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L7-ARA [auth L7],
SD [auth l7]
243Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 45
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L8-ASA [auth L8],
TD [auth l8]
255Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 46
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L9-ATA [auth L9],
UD [auth l9]
191Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
Find proteins for P05738 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c))
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Entity ID: 47
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L10UA [auth M0],
VD [auth m0]
220Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 48
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L11-BVA [auth M1],
WD [auth m1]
173Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 49
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L13-AWA [auth M3],
YD [auth m3]
198Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 50
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L14-AXA [auth M4],
ZD [auth m4]
137Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 51
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L15-AAE [auth m5],
YA [auth M5]
203Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 52
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L16-ABE [auth m6],
ZA [auth M6]
198Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 53
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L17-AAB [auth M7],
CE [auth m7]
183Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 54
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L18-ABB [auth M8],
DE [auth m8]
185Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 55
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L19-ACB [auth M9],
EE [auth m9]
188Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 56
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L20-ADB [auth N0],
FE [auth n0]
172Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 57
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L21-AEB [auth N1],
GE [auth n1]
159Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 58
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L22-AFB [auth N2],
HE [auth n2]
120Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 59
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L23-AGB [auth N3],
IE [auth n3]
136Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 60
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L24-AHB [auth N4],
JE [auth n4]
155Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 61
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L25IB [auth N5],
KE [auth n5]
141Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 62
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L26-AJB [auth N6],
LE [auth n6]
126Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 63
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L27-AKB [auth N7],
ME [auth n7]
135Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 64
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L28LB [auth N8],
NE [auth n8]
148Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 65
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L29MB [auth N9],
OE [auth n9]
58Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 66
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L30NB [auth O0],
PE [auth o0]
104Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 67
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L31-AOB [auth O1],
QE [auth o1]
112Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 68
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L32PB [auth O2],
RE [auth o2]
129Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 69
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L33-AQB [auth O3],
SE [auth o3]
106Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 70
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L34-ARB [auth O4],
TE [auth o4]
119Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 71
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L35-ASB [auth O5],
UE [auth o5]
119Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 72
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L36-ATB [auth O6],
VE [auth o6]
99Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 73
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L37-AUB [auth O7],
WE [auth o7]
87Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 74
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L38VB [auth O8],
XE [auth o8]
77Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 75
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L39WB [auth O9],
YE [auth o9]
50Saccharomyces cerevisiae S288CMutation(s): 0 
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Entity ID: 76
MoleculeChains Sequence LengthOrganismDetailsImage
Ubiquitin-60S ribosomal protein L40XB [auth Q0],
ZE [auth q0]
52Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 77
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L41-AAF [auth q1],
YB [auth Q1]
25Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 78
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L42-ABF [auth q2],
ZB [auth Q2]
105Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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Entity ID: 79
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L43-AAC [auth Q3],
CF [auth q3]
91Saccharomyces cerevisiae S288CMutation(s): 0 
UniProt
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