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protein dna_rna ligands metals Protein-protein interface(s) links
Ribosome PDB id
1k73
Jmol
Contents
Protein chains
237 a.a. *
337 a.a. *
246 a.a. *
140 a.a. *
172 a.a. *
119 a.a. *
29 a.a. *
156 a.a. *
142 a.a. *
132 a.a. *
145 a.a. *
194 a.a. *
186 a.a. *
115 a.a. *
143 a.a. *
95 a.a. *
150 a.a. *
81 a.a. *
119 a.a. *
53 a.a. *
65 a.a. *
154 a.a. *
82 a.a. *
142 a.a. *
73 a.a. *
56 a.a. *
46 a.a. *
92 a.a. *
DNA/RNA
Ligands
ANM
Metals
_CL ×22
_NA ×86
_MG ×117
_CD ×5
__K ×2
Waters ×7879
* Residue conservation analysis
PDB id:
1k73
Name: Ribosome
Title: Co-crystal structure of anisomycin bound to the 50s ribosomal subunit
Structure: 23s rrna. Chain: a. 5s rrna. Chain: b. Ribosomal protein l2. Chain: c. Synonym: 50s ribosomal protein l2p, hmal2, hl4. Ribosomal protein l3. Chain: d.
Source: Haloarcula marismortui. Organism_taxid: 2238. Organism_taxid: 2238
Biol. unit: 30mer (from PQS)
Resolution:
3.01Å     R-factor:   0.212     R-free:   0.246
Authors: J.Hansen,N.Ban,P.Nissen,P.B.Moore,T.A.Steitz
Key ref:
J.L.Hansen et al. (2003). Structures of five antibiotics bound at the peptidyl transferase center of the large ribosomal subunit. J Mol Biol, 330, 1061-1075. PubMed id: 12860128 DOI: 10.1016/S0022-2836(03)00668-5
Date:
18-Oct-01     Release date:   22-Jul-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P20276  (RL2_HALMA) -  50S ribosomal protein L2P
Seq:
Struc: 		240 a.a.
237 a.a.*
Protein chain
Pfam   ArchSchema ?
P20279  (RL3_HALMA) -  50S ribosomal protein L3P
Seq:
Struc: 		338 a.a.
337 a.a.
Protein chain
Pfam   ArchSchema ?
P12735  (RL4_HALMA) -  50S ribosomal protein L4P
Seq:
Struc: 		246 a.a.
246 a.a.*
Protein chain
Pfam   ArchSchema ?
P14124  (RL5_HALMA) -  50S ribosomal protein L5P
Seq:
Struc: 		177 a.a.
140 a.a.
Protein chain
Pfam   ArchSchema ?
P14135  (RL6_HALMA) -  50S ribosomal protein L6P
Seq:
Struc: 		178 a.a.
172 a.a.
Protein chain
Pfam   ArchSchema ?
P12743  (RL7A_HALMA) -  50S ribosomal protein L7Ae
Seq:
Struc: 		120 a.a.
119 a.a.*
Protein chain
Pfam   ArchSchema ?
P15825  (RLA0_HALMA) -  50S ribosomal protein L10E
Seq:
Struc: 		348 a.a.
29 a.a.*
Protein chain
Pfam   ArchSchema ?
P60617  (RL10_HALMA) -  50S ribosomal protein L10e
Seq:
Struc: 		177 a.a.
156 a.a.*
Protein chain
Pfam   ArchSchema ?
P29198  (RL13_HALMA) -  50S ribosomal protein L13P
Seq:
Struc: 		145 a.a.
142 a.a.
Protein chain
Pfam   ArchSchema ?
P22450  (RL14_HALMA) -  50S ribosomal protein L14P
Seq:
Struc: 		132 a.a.
132 a.a.
Protein chain
Pfam   ArchSchema ?
P12737  (RL15_HALMA) -  50S ribosomal protein L15P
Seq:
Struc: 		165 a.a.
145 a.a.
Protein chain
Pfam   ArchSchema ?
P60618  (RL15E_HALMA) -  50S ribosomal protein L15e
Seq:
Struc: 		196 a.a.
194 a.a.*
Protein chain
Pfam   ArchSchema ?
P14123  (RL18_HALMA) -  50S ribosomal protein L18P
Seq:
Struc: 		187 a.a.
186 a.a.
Protein chain
Pfam   ArchSchema ?
P12733  (RL18E_HALMA) -  50S ribosomal protein L18e
Seq:
Struc: 		116 a.a.
115 a.a.
Protein chain
Pfam   ArchSchema ?
P14119  (RL19_HALMA) -  50S ribosomal protein L19e
Seq:
Struc: 		149 a.a.
143 a.a.*
Protein chain
Pfam   ArchSchema ?
P12734  (RL21_HALMA) -  50S ribosomal protein L21e
Seq:
Struc: 		96 a.a.
95 a.a.
Protein chain
Pfam   ArchSchema ?
P10970  (RL22_HALMA) -  50S ribosomal protein L22P
Seq:
Struc: 		155 a.a.
150 a.a.
Protein chain
Pfam   ArchSchema ?
P12732  (RL23_HALMA) -  50S ribosomal protein L23P
Seq:
Struc: 		85 a.a.
81 a.a.
Protein chain
Pfam   ArchSchema ?
P10972  (RL24_HALMA) -  50S ribosomal protein L24P
Seq:
Struc: 		120 a.a.
119 a.a.
Protein chain
Pfam   ArchSchema ?
P14116  (RL24E_HALMA) -  50S ribosomal protein L24e
Seq:
Struc: 		67 a.a.
53 a.a.
Protein chain
Pfam   ArchSchema ?
P10971  (RL29_HALMA) -  50S ribosomal protein L29P
Seq:
Struc: 		71 a.a.
65 a.a.
Protein chain
Pfam   ArchSchema ?
P14121  (RL30_HALMA) -  50S ribosomal protein L30P
Seq:
Struc: 		154 a.a.
154 a.a.
Protein chain
Pfam   ArchSchema ?
P18138  (RL31_HALMA) -  50S ribosomal protein L31e
Seq:
Struc: 		92 a.a.
82 a.a.
Protein chain
Pfam   ArchSchema ?
P12736  (RL32_HALMA) -  50S ribosomal protein L32e
Seq:
Struc: 		241 a.a.
142 a.a.
Protein chain
Pfam   ArchSchema ?
P60619  (RL37A_HALMA) -  50S ribosomal protein L37Ae
Seq:
Struc: 		92 a.a.
73 a.a.*
Protein chain
Pfam   ArchSchema ?
P32410  (RL37_HALMA) -  50S ribosomal protein L37e
Seq:
Struc: 		57 a.a.
56 a.a.
Protein chain
Pfam   ArchSchema ?
P22452  (RL39_HALMA) -  50S ribosomal protein L39e
Seq:
Struc: 		50 a.a.
46 a.a.*
Protein chain
Pfam   ArchSchema ?
P32411  (RL44_HALMA) -  50S ribosomal protein L44E
Seq:
Struc: 		92 a.a.
92 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 185 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   4 terms 
  Biological process     ribosome biogenesis   3 terms 
  Biochemical function     structural constituent of ribosome     9 terms  

 

 
DOI no: 10.1016/S0022-2836(03)00668-5 J Mol Biol 330:1061-1075 (2003)
PubMed id: 12860128  
 
 
Structures of five antibiotics bound at the peptidyl transferase center of the large ribosomal subunit.
J.L.Hansen, P.B.Moore, T.A.Steitz.
 
  ABSTRACT  
 
Structures of anisomycin, chloramphenicol, sparsomycin, blasticidin S, and virginiamycin M bound to the large ribosomal subunit of Haloarcula marismortui have been determined at 3.0A resolution. Most of these antibiotics bind to sites that overlap those of either peptidyl-tRNA or aminoacyl-tRNA, consistent with their functioning as competitive inhibitors of peptide bond formation. Two hydrophobic crevices, one at the peptidyl transferase center and the other at the entrance to the peptide exit tunnel play roles in binding these antibiotics. Midway between these crevices, nucleotide A2103 of H.marismortui (2062 Escherichia coli) varies in its conformation and thereby contacts antibiotics bound at either crevice. The aromatic ring of anisomycin binds to the active-site hydrophobic crevice, as does the aromatic ring of puromycin, while the aromatic ring of chloramphenicol binds to the exit tunnel hydrophobic crevice. Sparsomycin contacts primarily a P-site bound substrate, but also extends into the active-site hydrophobic crevice. Virginiamycin M occupies portions of both the A and P-site, and induces a conformational change in the ribosome. Blasticidin S base-pairs with the P-loop and thereby mimics C74 and C75 of a P-site bound tRNA.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Electron density maps. Unbiased F[o] -F[c] difference Fourier maps (gray netting) contoured at 3.0s reveal the location, orientation, and conformation of these antibiotics. (a), (b) Nucleotides of ribosomal RNA (gray sticks) that are either protected or deprotected by the anisomycin (a) or chloramphenicol (b) from chemical modification (green) or that upon mutation confer resistance to the given antibiotic (orange) are provided for context. (c) The placement and conformation of virginiamycin M (blue) in the corresponding doughnut shaped electron density is unambiguous. (d) Blasticidin S (purple) binds at two sites, but density for the second site is weaker and incomplete. (e) Sparsomycin (green) binds only in the presence of a P-site bound substrate (orange). A2637 (2602) (gray stick) is apparent in the difference map because it changes conformation upon substrate binding. 		Figure 7.
Figure 7. Sparsomycin binding site. Sparsomycin (green) is sandwiched between the CCA end of P-site bound substrate analogue, CCA-phe-cap-biotin (large spheres) and the base of A2637 (2602) (gray sticks). Hydrogen bonds and ionic interactions are shown as dotted lines. A magnesium ion is purple and water molecules are small red spheres. The sulfur (yellow) containing tail of sparsomycin enters the active-site hydrophobic crevice between A2486 (2451) (gray sticks) and C2487 (2452) (orange sticks, resistance mutation).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 330, 1061-1075) copyright 2003.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21513713 A.Fabbretti, C.O.Gualerzi, and L.Brandi (2011).
How to cope with the quest for new antibiotics.
  FEBS Lett, 585, 1673-1681.  
21356104 R.E.Valas, and P.E.Bourne (2011).
The origin of a derived superkingdom: how a gram-positive bacterium crossed the desert to become an archaeon.
  Biol Direct, 6, 16.  
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.  
20876128 J.A.Dunkle, L.Xiong, A.S.Mankin, and J.H.Cate (2010).
Structures of the Escherichia coli ribosome with antibiotics bound near the peptidyl transferase center explain spectra of drug action.
  Proc Natl Acad Sci U S A, 107, 17152-17157.
PDB codes: 3oaq 3oar 3oas 3oat 3ofa 3ofb 3ofc 3ofd 3ofo 3ofp 3ofq 3ofr 3ofx 3ofy 3ofz 3og0
20464003 J.Piel (2010).
Biosynthesis of polyketides by trans-AT polyketide synthases.
  Nat Prod Rep, 27, 996.  
20705654 M.H.Rhodin, and J.D.Dinman (2010).
A flexible loop in yeast ribosomal protein L11 coordinates P-site tRNA binding.
  Nucleic Acids Res, 38, 8377-8389.  
20822442 M.Morar, and G.D.Wright (2010).
The genomic enzymology of antibiotic resistance.
  Annu Rev Genet, 44, 25-51.  
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
20151411 X.Ge, and B.Roux (2010).
Calculation of the standard binding free energy of sparsomycin to the ribosomal peptidyl-transferase P-site using molecular dynamics simulations with restraining potentials.
  J Mol Recognit, 23, 128-141.  
19465765 D.M.Pettigrew, P.Roversi, S.G.Davies, A.J.Russell, and S.M.Lea (2009).
A structural study of the interaction between the Dr haemagglutinin DraE and derivatives of chloramphenicol.
  Acta Crystallogr D Biol Crystallogr, 65, 513-522.
PDB codes: 2jkj 2jkl 2jkn 2w5p
19929179 D.N.Wilson (2009).
The A-Z of bacterial translation inhibitors.
  Crit Rev Biochem Mol Biol, 44, 393-433.  
19019162 E.Diago-Navarro, L.Mora, R.H.Buckingham, R.Díaz-Orejas, and M.Lemonnier (2009).
Novel Escherichia coli RF1 mutants with decreased translation termination activity and increased sensitivity to the cytotoxic effect of the bacterial toxins Kid and RelE.
  Mol Microbiol, 71, 66-78.  
19089882 E.Zimmerman, and A.Yonath (2009).
Biological implications of the ribosome's stunning stereochemistry.
  Chembiochem, 10, 63-72.  
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
19170872 H.Ramu, A.Mankin, and N.Vazquez-Laslop (2009).
Programmed drug-dependent ribosome stalling.
  Mol Microbiol, 71, 811-824.  
20007368 J.E.McLaughlin, M.A.Bin-Umer, A.Tortora, N.Mendez, S.McCormick, and N.E.Tumer (2009).
A genome-wide screen in Saccharomyces cerevisiae reveals a critical role for the mitochondria in the toxicity of a trichothecene mycotoxin.
  Proc Natl Acad Sci U S A, 106, 21883-21888.  
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.  
19284290 R.Kodym, E.Kodym, and M.D.Story (2009).
Short double-stranded RNAs of specific sequence activate ribosomal TAK1-D and induce a global inhibition of translation.
  Biol Chem, 390, 453-462.  
  19173642 S.Shoji, S.E.Walker, and K.Fredrick (2009).
Ribosomal translocation: one step closer to the molecular mechanism.
  ACS Chem Biol, 4, 93.  
18263608 A.Meskauskas, J.R.Russ, and J.D.Dinman (2008).
Structure/function analysis of yeast ribosomal protein L2.
  Nucleic Acids Res, 36, 1826-1835.  
18824477 A.N.Petrov, A.Meskauskas, S.C.Roshwalb, and J.D.Dinman (2008).
Yeast ribosomal protein L10 helps coordinate tRNA movement through the large subunit.
  Nucleic Acids Res, 36, 6187-6198.  
18636557 A.Vourekas, V.Stamatopoulou, C.Toumpeki, M.Tsitlaidou, and D.Drainas (2008).
Insights into functional modulation of catalytic RNA activity.
  IUBMB Life, 60, 669-683.  
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.  
18060665 C.Foster, and W.S.Champney (2008).
Characterization of a 30S ribosomal subunit assembly intermediate found in Escherichia coli cells growing with neomycin or paromomycin.
  Arch Microbiol, 189, 441-449.  
18282091 D.L.Theobald, and D.S.Wuttke (2008).
Accurate structural correlations from maximum likelihood superpositions.
  PLoS Comput Biol, 4, e43.  
18757750 D.N.Wilson, F.Schluenzen, J.M.Harms, A.L.Starosta, S.R.Connell, and P.Fucini (2008).
The oxazolidinone antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning.
  Proc Natl Acad Sci U S A, 105, 13339-13344.
PDB code: 3dll
18824514 D.Rodriguez-Correa, and A.E.Dahlberg (2008).
Kinetic and thermodynamic studies of peptidyltransferase in ribosomes from the extreme thermophile Thermus thermophilus.
  RNA, 14, 2314-2318.  
18663023 E.Skripkin, T.S.McConnell, J.DeVito, L.Lawrence, J.A.Ippolito, E.M.Duffy, J.Sutcliffe, and F.Franceschi (2008).
R chi-01, a new family of oxazolidinones that overcome ribosome-based linezolid resistance.
  Antimicrob Agents Chemother, 52, 3550-3557.  
18455733 G.Blaha, G.Gürel, S.J.Schroeder, P.B.Moore, and T.A.Steitz (2008).
Mutations outside the anisomycin-binding site can make ribosomes drug-resistant.
  J Mol Biol, 379, 505-519.
PDB codes: 3cc2 3cc4 3cc7 3cce 3ccj 3ccl 3ccm 3ccq 3ccr 3ccs 3ccu 3ccv 3cd6
18936244 H.Ishida, and S.Hayward (2008).
Path of nascent polypeptide in exit tunnel revealed by molecular dynamics simulation of ribosome.
  Biophys J, 95, 5962-5973.  
18256246 J.Esguerra, J.Warringer, and A.Blomberg (2008).
Functional importance of individual rRNA 2'-O-ribose methylations revealed by high-resolution phenotyping.
  RNA, 14, 649-656.  
18299405 L.K.Smith, and A.S.Mankin (2008).
Transcriptional and translational control of the mlr operon, which confers resistance to seven classes of protein synthesis inhibitors.
  Antimicrob Agents Chemother, 52, 1703-1712.  
18568365 M.C.Frigieri, M.V.João Luiz, L.H.Apponi, C.F.Zanelli, and S.R.Valentini (2008).
Synthetic lethality between eIF5A and Ypt1 reveals a connection between translation and the secretory pathway in yeast.
  Mol Genet Genomics, 280, 211-221.  
18205815 R.Elevi Bardavid, and A.Oren (2008).
Sensitivity of Haloquadratum and Salinibacter to antibiotics and other inhibitors: implications for the assessment of the contribution of Archaea and Bacteria to heterotrophic activities in hypersaline environments.
  FEMS Microbiol Ecol, 63, 309-315.  
18203742 R.Rakauskaite, and J.D.Dinman (2008).
rRNA mutants in the yeast peptidyltransferase center reveal allosteric information networks and mechanisms of drug resistance.
  Nucleic Acids Res, 36, 1497-1507.  
18382121 T.A.Steitz (2008).
Structural insights into the functions of the large ribosomal subunit, a major antibiotic target.
  Keio J Med, 57, 1.  
17401565 X.Wang, G.Kapral, L.Murray, D.Richardson, J.Richardson, and J.Snoeyink (2008).
RNABC: forward kinematics to reduce all-atom steric clashes in RNA backbone.
  J Math Biol, 56, 253-278.  
17386264 A.Meskauskas, and J.D.Dinman (2007).
Ribosomal protein L3: gatekeeper to the A site.
  Mol Cell, 25, 877-888.