7Q08

Structure of Candida albicans 80S ribosome in complex with cycloheximide


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 2.56 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

E-site drug specificity of the human pathogen Candida albicans ribosome.

Zgadzay, Y.Kolosova, O.Stetsenko, A.Wu, C.Bruchlen, D.Usachev, K.Validov, S.Jenner, L.Rogachev, A.Yusupova, G.Sachs, M.S.Guskov, A.Yusupov, M.

(2022) Sci Adv 8: eabn1062-eabn1062

  • DOI: https://doi.org/10.1126/sciadv.abn1062
  • Primary Citation of Related Structures:  
    7PZY, 7Q08, 7Q0F, 7Q0P, 7Q0R

  • PubMed Abstract: 

    Candida albicans is a widespread commensal fungus with substantial pathogenic potential and steadily increasing resistance to current antifungal drugs. It is known to be resistant to cycloheximide (CHX) that binds to the E-transfer RNA binding site of the ribosome. Because of lack of structural information, it is neither possible to understand the nature of the resistance nor to develop novel inhibitors. To overcome this issue, we determined the structure of the vacant C. albicans 80 S ribosome at 2.3 angstroms and its complexes with bound inhibitors at resolutions better than 2.9 angstroms using cryo-electron microscopy. Our structures reveal how a change in a conserved amino acid in ribosomal protein eL42 explains CHX resistance in C. albicans and forms a basis for further antifungal drug development.


  • Organizational Affiliation

    Department of Integrated Structural Biology, Institute of Genetics and Molecular and Cellular Biology, University of Strasbourg, Illkirch, France.


Macromolecules

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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L2AD [auth j]254Candida albicans SC5314Mutation(s): 0 
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L3E [auth k]389Candida albicans SC5314Mutation(s): 0 
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Entity ID: 6
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L4BF [auth l]363Candida albicans SC5314Mutation(s): 0 
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Entity ID: 7
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L5G [auth m]298Candida albicans SC5314Mutation(s): 0 
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Entity ID: 8
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L6H [auth n]176Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PCX8 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 9
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L7AI [auth o]241Candida albicans SC5314Mutation(s): 0 
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Entity ID: 10
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L8J [auth p]262Candida albicans SC5314Mutation(s): 0 
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Entity ID: 11
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L9BK [auth q]191Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 12
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L10L [auth r]220Candida albicans SC5314Mutation(s): 0 
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Entity ID: 13
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L11BM [auth s]174Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 14
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L13N [auth t]202Candida albicans SC5314Mutation(s): 0 
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Find proteins for O59931 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 15
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L14BO [auth u]131Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PFL9 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 16
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal protein L15P [auth v]204Candida albicans SC5314Mutation(s): 0 
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Entity ID: 17
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L16AQ [auth w]200Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 18
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L17BR [auth x]185Candida albicans SC5314Mutation(s): 0 
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Entity ID: 19
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L18AS [auth y]186Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PK43 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 20
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal protein L19T [auth z]190Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PK40 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 21
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L20U [auth 0]172Candida albicans SC5314Mutation(s): 0 
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Find proteins for A0A1D8PLC9 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 22
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L21AV [auth 2]160Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PGY0 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 23
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L22BW [auth 5]124Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PM41 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 24
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L23BX [auth 6]137Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 25
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L24AY [auth 7]155Candida albicans SC5314Mutation(s): 0 
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Entity ID: 26
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L25Z [auth 8]142Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 27
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L26BAA [auth 9]127Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 28
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L27BA [auth AA]136Candida albicans SC5314Mutation(s): 0 
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Entity ID: 29
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L28CA [auth AB]149Candida albicans SC5314Mutation(s): 0 
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Entity ID: 30
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L29DA [auth AC]63Candida albicans SC5314Mutation(s): 0 
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Entity ID: 31
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L30EA [auth AD]106Candida albicans SC5314Mutation(s): 0 
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Entity ID: 32
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L31BFA [auth AE]112Candida albicans SC5314Mutation(s): 0 
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Entity ID: 33
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L32GA [auth AF]131Candida albicans SC5314Mutation(s): 0 
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Entity ID: 34
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L33AHA [auth AG]107Candida albicans SC5314Mutation(s): 0 
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Entity ID: 35
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L34BIA [auth AH]122Candida albicans SC5314Mutation(s): 0 
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Entity ID: 36
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L35AJA [auth AI]120Candida albicans SC5314Mutation(s): 0 
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Entity ID: 37
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L36KA [auth AJ]99Candida albicans SC5314Mutation(s): 0 
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Find proteins for A0A1D8PH21 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 38
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal protein L37LA [auth AK]90Candida albicans SC5314Mutation(s): 0 
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Find proteins for A0A1D8PF45 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 39
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L38MA [auth AL]78Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 40
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein L39NA [auth AM]51Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 41
MoleculeChains Sequence LengthOrganismDetailsImage
Rpl40bpOA [auth AN]52Candida albicans SC5314Mutation(s): 0 
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Find proteins for A0A1D8PL68 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 42
MoleculeChains Sequence LengthOrganismDetailsImage
60S ribosomal protein eL41PA [auth AO]25Candida albicans SC5314Mutation(s): 0 
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Entity ID: 43
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L42AQA [auth AP]106Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PEV4 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 44
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 60S subunit protein L43ARA [auth AQ]92Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PP14 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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UniProt GroupA0A1D8PP14
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Entity ID: 45
MoleculeChains Sequence LengthOrganismDetailsImage
HABP4_PAI-RBP1 domain-containing proteinSA [auth i]267Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PK71 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 47
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S0UA [auth B]261Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for O42817 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 48
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S1VA [auth C]256Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for P40910 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 49
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 40S subunit protein S2WA [auth D]249Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for Q5A900 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 50
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 40S subunit protein S3XA [auth E]251Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PSV5 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 51
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S4YA [auth F]262Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 52
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 40S subunit protein S5ZA [auth G]225Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 53
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S6AB [auth H]236Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PL99 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 54
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S7BB [auth I]186Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 55
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S8CB [auth J]206Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 56
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 40S subunit protein S9BDB [auth K]189Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 57
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 40S subunit protein S10AEB [auth L]118Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 58
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 40S subunit protein S11AFB [auth M]155Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PN83 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 59
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S12GB [auth N]143Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 60
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 40S subunit protein S13HB [auth O]151Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 61
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 40S subunit protein S14BIB [auth P]132Candida albicans SC5314Mutation(s): 1 
UniProt
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Entity ID: 62
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 40S subunit protein S15JB [auth Q]142Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PK22 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 63
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 40S subunit protein S16AKB [auth R]142Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 64
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 40S subunit protein S17BLB [auth S]137Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PEY9 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 65
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 40S subunit protein S18BMB [auth T]145Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PQQ5 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 66
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 40S subunit protein S19ANB [auth U]145Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PK61 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 67
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 40S subunit protein S20OB [auth V]119Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for Q5A389 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 68
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S21PB [auth W]87Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PCG7 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 69
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S22-AQB [auth X]130Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 70
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 40S subunit protein S23BRB [auth Y]145Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 71
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S24SB [auth Z]135Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for Q5A7K0 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 72
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S25TB [auth a]105Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PNQ6 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 73
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S26UB [auth b]119Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for Q5ALV6 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 74
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S27VB [auth c]82Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 75
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 40S subunit protein S28BWB [auth d]67Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 76
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal 40S subunit protein S29AXB [auth e]56Candida albicans SC5314Mutation(s): 0 
UniProt
Find proteins for A0A1D8PTR4 (Candida albicans (strain SC5314 / ATCC MYA-2876))
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Entity ID: 77
MoleculeChains Sequence LengthOrganismDetailsImage
40S ribosomal protein S30YB [auth f]63Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 78
MoleculeChains Sequence LengthOrganismDetailsImage
Ubiquitin-ribosomal 40S subunit protein S31 fusion proteinZB [auth g]193Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 79
MoleculeChains Sequence LengthOrganismDetailsImage
Guanine nucleotide-binding protein subunit beta-like proteinAC [auth h]317Candida albicans SC5314Mutation(s): 0 
UniProt
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Entity ID: 1
MoleculeChains LengthOrganismImage
25S ribosomal RNAA [auth 1]3,359Candida albicans SC5314
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Entity ID: 2
MoleculeChains LengthOrganismImage
5S ribosomal RNAB [auth 3]121Candida albicans SC5314
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Entity ID: 3
MoleculeChains LengthOrganismImage
5.8S ribosomal RNAC [auth 4]158Candida albicans SC5314
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Entity ID: 46
MoleculeChains LengthOrganismImage
18S ribosomal RNATA [auth A]1,787Candida albicans SC5314
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Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
3HE (Subject of Investigation/LOI)
Query on 3HE

Download Ideal Coordinates CCD File 
CC [auth 1]4-{(2R)-2-[(1S,3S,5S)-3,5-dimethyl-2-oxocyclohexyl]-2-hydroxyethyl}piperidine-2,6-dione
C15 H23 N O4
YPHMISFOHDHNIV-FSZOTQKASA-N
SPD
Query on SPD

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BC [auth 1]SPERMIDINE
C7 H19 N3
ATHGHQPFGPMSJY-UHFFFAOYSA-N
ZN
Query on ZN

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DC [auth AK]
EC [auth AN]
FC [auth AP]
GC [auth AQ]
HC [auth b]
DC [auth AK],
EC [auth AN],
FC [auth AP],
GC [auth AQ],
HC [auth b],
IC [auth c],
JC [auth e],
KC [auth g]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MLZ
Query on MLZ
X [auth 6]L-PEPTIDE LINKINGC7 H16 N2 O2LYS
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 2.56 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Russian Science FoundationFrance20-65-47031
Russian Science FoundationFrance20-64-47041
Foundation for Medical Research (France)FranceFDT202106012811
Foundation for Medical Research (France)FranceDEQ20181039600
Foundation for Medical Research (France)FranceDBF20160635745

Revision History  (Full details and data files)

  • Version 1.0: 2022-05-25
    Type: Initial release
  • Version 1.1: 2022-06-08
    Changes: Database references