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PDBsum entry 3dll
Go to PDB code: 
protein dna_rna ligands metals Protein-protein interface(s) links
Ribosome PDB id
3dll
Contents
Protein chains
218 a.a. *
205 a.a. *
197 a.a. *
177 a.a. *
171 a.a. *
70 a.a. *
142 a.a. *
134 a.a. *
141 a.a. *
136 a.a. *
113 a.a. *
104 a.a. *
108 a.a. *
117 a.a. *
94 a.a. *
127 a.a. *
93 a.a. *
110 a.a. *
175 a.a. *
84 a.a. *
72 a.a. *
66 a.a. *
55 a.a. *
58 a.a. *
53 a.a.* *
46 a.a.* *
63 a.a.* *
37 a.a. *
DNA/RNA
Ligands
ZLD
Metals
_MG ×35
_ZN ×2
* Residue conservation analysis
* C-alpha coords only
PDB id:
3dll
Name: Ribosome
Title: The oxazolidinone antibiotics perturb the ribosomal peptidyl- transferase center and effect tRNA positioning
Structure: Rrna-23s ribosomal RNA. Chain: x. Rrna-5s ribosomal RNA. Chain: z. 50s ribosomal protein l2. Chain: a. 50s ribosomal protein l3. Chain: b. 50s ribosomal protein l4.
Source: Deinococcus radiodurans. Organism_taxid: 1299. Organism_taxid: 1299
Resolution:
3.50Å     R-factor:   0.259     R-free:   0.280
Authors: D.N.Wilson,F.Schluenzen,J.M.Harms,A.L.Starosta,S.R.Connell,P.Fucini
Key ref:
D.N.Wilson et al. (2008). The oxazolidinone antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning. Proc Natl Acad Sci U S A, 105, 13339-13344. PubMed id: 18757750 DOI: 10.1073/pnas.0804276105
Date:
27-Jun-08     Release date:   16-Sep-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9RXJ9  (RL2_DEIRA) -  Large ribosomal subunit protein uL2 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		275 a.a.
218 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXK2  (RL3_DEIRA) -  Large ribosomal subunit protein uL3 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		211 a.a.
205 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXK1  (RL4_DEIRA) -  Large ribosomal subunit protein uL4 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		205 a.a.
197 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXJ0  (RL5_DEIRA) -  Large ribosomal subunit protein uL5 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		180 a.a.
177 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSL3  (RL6_DEIRA) -  Large ribosomal subunit protein uL6 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		185 a.a.
171 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSS7  (RL11_DEIRA) -  Large ribosomal subunit protein uL11 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		144 a.a.
70 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXY1  (RL13_DEIRA) -  Large ribosomal subunit protein uL13 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		174 a.a.
142 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXJ2  (RL14_DEIRA) -  Large ribosomal subunit protein uL14 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		134 a.a.
134 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSK9  (RL15_DEIRA) -  Large ribosomal subunit protein uL15 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		156 a.a.
141 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXJ5  (RL16_DEIRA) -  Large ribosomal subunit protein uL16 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		141 a.a.
136 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSJ5  (RL17_DEIRA) -  Large ribosomal subunit protein bL17 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		116 a.a.
113 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSL2  (RL18_DEIRA) -  Large ribosomal subunit protein uL18 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		114 a.a.
104 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RWB4  (RL19_DEIRA) -  Large ribosomal subunit protein bL19 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		166 a.a.
108 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSW7  (RL20_DEIRA) -  Large ribosomal subunit protein bL20 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		118 a.a.
117 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RY64  (RL21_DEIRA) -  Large ribosomal subunit protein bL21 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		100 a.a.
94 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXJ7  (RL22_DEIRA) -  Large ribosomal subunit protein uL22 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		134 a.a.
127 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXK0  (RL23_DEIRA) -  Large ribosomal subunit protein uL23 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		95 a.a.
93 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXJ1  (RL24_DEIRA) -  Large ribosomal subunit protein uL24 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		115 a.a.
110 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RX88  (RL25_DEIRA) -  Large ribosomal subunit protein bL25 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		237 a.a.
175 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RY65  (RL27_DEIRA) -  Large ribosomal subunit protein bL27 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		91 a.a.
84 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RRG8  (RL28_DEIRA) -  Large ribosomal subunit protein bL28 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		81 a.a.
72 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXJ4  (RL29_DEIRA) -  Large ribosomal subunit protein uL29 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		67 a.a.
66 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSL0  (RL30_DEIRA) -  Large ribosomal subunit protein uL30 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		55 a.a.
55 a.a.
Protein chain
Pfam   ArchSchema ?
P49228  (RL32_DEIRA) -  Large ribosomal subunit protein bL32 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		60 a.a.
58 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSS4  (RL33_DEIRA) -  Large ribosomal subunit protein bL33 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		55 a.a.
53 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSH2  (RL34_DEIRA) -  Large ribosomal subunit protein bL34 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		47 a.a.
46 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSW6  (RL35_DEIRA) -  Large ribosomal subunit protein bL35 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		66 a.a.
63 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSK0  (RL36_DEIRA) -  Large ribosomal subunit protein bL36 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		37 a.a.
37 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

DNA/RNA chains
  G-G-U-C-A-A-G-A-U-A-G-U-A-A-G-G-G-U-C-C-A-C-G-G-U-G-G-A-U-G-C-C-C-U-G-G-C-G-C- ... 2686 bases
  C-A-C-C-C-C-C-G-U-G-C-C-C-A-U-A-G-C-A-C-U-G-U-G-G-A-A-C-C-A-C-C-C-C-A-C-C-C-C- 122 bases

 

 
    reference    
 
 
DOI no: 10.1073/pnas.0804276105 Proc Natl Acad Sci U S A 105:13339-13344 (2008)
PubMed id: 18757750  
 
 
The oxazolidinone antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning.
D.N.Wilson, F.Schluenzen, J.M.Harms, A.L.Starosta, S.R.Connell, P.Fucini.
 
  ABSTRACT  
 
The oxazolidinones represent the first new class of antibiotics to enter into clinical usage within the past 30 years, but their binding site and mechanism of action has not been fully characterized. We have determined the crystal structure of the oxazolidinone linezolid bound to the Deinococcus radiodurans 50S ribosomal subunit. Linezolid binds in the A site pocket at the peptidyltransferase center of the ribosome overlapping the aminoacyl moiety of an A-site bound tRNA as well as many clinically important antibiotics. Binding of linezolid stabilizes a distinct conformation of the universally conserved 23S rRNA nucleotide U2585 that would be nonproductive for peptide bond formation. In conjunction with available biochemical data, we present a model whereby oxazolidinones impart their inhibitory effect by perturbing the correct positioning of tRNAs on the ribosome.
 
  Selected figure(s)  
 
Figure 1.
The binding site of oxazolidinones. (A) Secondary structure of the peptidyltransferase ring of the 23S rRNA from D. radiodurans with the mutation sites in bacteria (blue) and archaea (purple) that confer resistance to oxazolidinones indicated with E. coli numbering. Nucleotides that directly interact with linezolid are shaded light blue, and the mutations sites associated with resistance for chloramphenicol (cam) (45, 46), anisomycin (aniso) (47, 48), and pleuromutilins (pleuro) (49) are shown. (B) Interface view of the D. radiodurans 50S subunit with the binding position of linezolid (red) and landmark proteins L1 and L11 as indicated. (C) Chemical structure of linezolid, highlighting the three aromatic rings (A–C) and the acetamidomethyl tail. (D) View of linezolid (pink) within the binding pocket formed by eight universally conserved nucleotides (blue) of the 23S rRNA. The arrow indicates tunnel direction. 		Figure 4.
Linezolid overlaps A-site ligands at the peptidyltransferase center. (A–F) Comparison of the binding site of linezolid (pink) on D50S (A) with chloramphenicol (PDB ID code 1K01; green) (6) (B), anisomycin (PDB ID code 1K73; olive) (3) (C), tiamulin (PDB ID code 1XBP; teal) (7) (D), clindamycin (PDB ID code 1JZX; magenta) (6) (E), and A- (yellow) and P-site (orange) phenylalanyl-tRNA CCA-end mimics (PDB ID code 1VQN) (27) (F). In all cases, U2585 (blue) from the D50S-linezolid structure is shown for reference.
 
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22421879 C.A.Arias, and B.E.Murray (2012).
The rise of the Enterococcus: beyond vancomycin resistance.
  Nat Rev Microbiol, 10, 266-278.  
21513713 A.Fabbretti, C.O.Gualerzi, and L.Brandi (2011).
How to cope with the quest for new antibiotics.
  FEBS Lett, 585, 1673-1681.  
21701501 D.C.Swinney, and J.Anthony (2011).
How were new medicines discovered?
  Nat Rev Drug Discov, 10, 507-519.  
  21434942 K.L.Leach, S.J.Brickner, M.C.Noe, and P.F.Miller (2011).
Linezolid, the first oxazolidinone antibacterial agent.
  Ann N Y Acad Sci, 1222, 49-54.  
20455685 A.R.Renslo (2010).
Antibacterial oxazolidinones: emerging structure-toxicity relationships.
  Expert Rev Anti Infect Ther, 8, 565-574.  
20385807 D.B.Johnson, and L.Wang (2010).
Imprints of the genetic code in the ribosome.
  Proc Natl Acad Sci U S A, 107, 8298-8303.  
20494981 H.David-Eden, A.S.Mankin, and Y.Mandel-Gutfreund (2010).
Structural signatures of antibiotic binding sites on the ribosome.
  Nucleic Acids Res, 38, 5982-5994.  
20348931 J.C.Velez, and M.G.Janech (2010).
A case of lactic acidosis induced by linezolid.
  Nat Rev Nephrol, 6, 236-242.  
20080686 T.Auerbach, I.Mermershtain, C.Davidovich, A.Bashan, M.Belousoff, I.Wekselman, E.Zimmerman, L.Xiong, D.Klepacki, K.Arakawa, H.Kinashi, A.S.Mankin, and A.Yonath (2010).
The structure of ribosome-lankacidin complex reveals ribosomal sites for synergistic antibiotics.
  Proc Natl Acad Sci U S A, 107, 1983-1988.
PDB code: 3jq4
19144912 A.M.Giessing, S.S.Jensen, A.Rasmussen, L.H.Hansen, A.Gondela, K.Long, B.Vester, and F.Kirpekar (2009).
Identification of 8-methyladenosine as the modification catalyzed by the radical SAM methyltransferase Cfr that confers antibiotic resistance in bacteria.
  RNA, 15, 327-336.  
  19929179 D.N.Wilson (2009).
The A-Z of bacterial translation inhibitors.
  Crit Rev Biochem Mol Biol, 44, 393-433.  
19362093 G.Gürel, G.Blaha, P.B.Moore, and T.A.Steitz (2009).
U2504 determines the species specificity of the A-site cleft antibiotics: the structures of tiamulin, homoharringtonine, and bruceantin bound to the ribosome.
  J Mol Biol, 389, 146-156.
PDB codes: 3g4s 3g6e 3g71
19738021 G.Gürel, G.Blaha, T.A.Steitz, and P.B.Moore (2009).
Structures of triacetyloleandomycin and mycalamide A bind to the large ribosomal subunit of Haloarcula marismortui.
  Antimicrob Agents Chemother, 53, 5010-5014.
PDB codes: 3i55 3i56
19752277 J.B.Locke, M.Hilgers, and K.J.Shaw (2009).
Novel ribosomal mutations in Staphylococcus aureus strains identified through selection with the oxazolidinones linezolid and torezolid (TR-700).
  Antimicrob Agents Chemother, 53, 5265-5274.  
19805557 J.B.Locke, M.Hilgers, and K.J.Shaw (2009).
Mutations in ribosomal protein L3 are associated with oxazolidinone resistance in staphylococci of clinical origin.
  Antimicrob Agents Chemother, 53, 5275-5278.  
19351617 J.Feng, A.Lupien, H.Gingras, J.Wasserscheid, K.Dewar, D.Légaré, and M.Ouellette (2009).
Genome sequencing of linezolid-resistant Streptococcus pneumoniae mutants reveals novel mechanisms of resistance.
  Genome Res, 19, 1214-1223.  
19620335 K.L.LaPlante, and G.Sakoulas (2009).
Evaluating aztreonam and ceftazidime pharmacodynamics with Escherichia coli in combination with daptomycin, linezolid, or vancomycin in an in vitro pharmacodynamic model.
  Antimicrob Agents Chemother, 53, 4549-4555.  
19154331 K.S.Long, J.Poehlsgaard, L.H.Hansen, S.N.Hobbie, E.C.Böttger, and B.Vester (2009).
Single 23S rRNA mutations at the ribosomal peptidyl transferase centre confer resistance to valnemulin and other antibiotics in Mycobacterium smegmatis by perturbation of the drug binding pocket.
  Mol Microbiol, 71, 1218-1227.  
19741022 M.de la Peña, D.Dufour, and J.Gallego (2009).
Three-way RNA junctions with remote tertiary contacts: a recurrent and highly versatile fold.
  RNA, 15, 1949-1964.  
19075051 V.Kalia, R.Miglani, K.P.Purnapatre, T.Mathur, S.Singhal, S.Khan, S.R.Voleti, D.J.Upadhyay, K.S.Saini, A.Rattan, and V.S.Raj (2009).
Mode of action of Ranbezolid against staphylococci and structural modeling studies of its interaction with ribosomes.
  Antimicrob Agents Chemother, 53, 1427-1433.  
19098107 C.Davidovich, A.Bashan, and A.Yonath (2008).
Structural basis for cross-resistance to ribosomal PTC antibiotics.
  Proc Natl Acad Sci U S A, 105, 20665-20670.  
19006597 P.L.Taylor, and G.D.Wright (2008).
Novel approaches to discovery of antibacterial agents.
  Anim Health Res Rev, 9, 237-246.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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