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PDBsum entry 1nwx

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protein dna_rna ligands links
Ribosome PDB id
1nwx
Jmol
Contents
Protein chains
270 a.a.* *
205 a.a.* *
197 a.a.* *
178 a.a.* *
177 a.a.* *
52 a.a.* *
143 a.a.* *
143 a.a.* *
132 a.a.* *
141 a.a.* *
124 a.a.* *
114 a.a.* *
111 a.a.* *
125 a.a.* *
117 a.a.* *
100 a.a.* *
130 a.a.* *
93 a.a.* *
113 a.a.* *
223 a.a.* *
86 a.a.* *
65 a.a.* *
55 a.a.* *
73 a.a.* *
58 a.a.* *
53 a.a.* *
46 a.a.* *
63 a.a.* *
35 a.a.* *
DNA/RNA
Ligands
773
* Residue conservation analysis
* C-alpha coords only
PDB id:
1nwx
Name: Ribosome
Title: Complex of the large ribosomal subunit from deinococcus radiodurans with abt-773
Structure: 23s ribosomal RNA. Chain: 0. 5s ribosomal RNA. Chain: 9. Ribosomal protein l2. Chain: a. Ribosomal protein l3. Chain: b. Ribosomal protein l4.
Source: Deinococcus radiodurans. Organism_taxid: 1299. Organism_taxid: 1299
Biol. unit: 31mer (from PQS)
Resolution:
3.50Å     R-factor:   0.285     R-free:   0.313
Authors: F.Schluenzen,J.Harms,F.Franceschi,H.A.S.Hansen,H.Bartels, R.Zarivach,A.Yonath
Key ref:
F.Schlünzen et al. (2003). Structural basis for the antibiotic activity of ketolides and azalides. Structure, 11, 329-338. PubMed id: 12623020 DOI: 10.1016/S0969-2126(03)00022-4
Date:
07-Feb-03     Release date:   18-Mar-03    
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9RXJ9  (RL2_DEIRA) -  50S ribosomal protein L2
Seq:
Struc:
275 a.a.
270 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXK2  (RL3_DEIRA) -  50S ribosomal protein L3
Seq:
Struc:
211 a.a.
205 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXK1  (RL4_DEIRA) -  50S ribosomal protein L4
Seq:
Struc:
205 a.a.
197 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXJ0  (RL5_DEIRA) -  50S ribosomal protein L5
Seq:
Struc:
180 a.a.
178 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSL3  (RL6_DEIRA) -  50S ribosomal protein L6
Seq:
Struc:
185 a.a.
177 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RY49  (RL9_DEIRA) -  50S ribosomal protein L9
Seq:
Struc:
146 a.a.
52 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSS7  (RL11_DEIRA) -  50S ribosomal protein L11
Seq:
Struc:
144 a.a.
143 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXY1  (RL13_DEIRA) -  50S ribosomal protein L13
Seq:
Struc:
174 a.a.
143 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXJ2  (RL14_DEIRA) -  50S ribosomal protein L14
Seq:
Struc:
134 a.a.
132 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSK9  (RL15_DEIRA) -  50S ribosomal protein L15
Seq:
Struc:
156 a.a.
141 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXJ5  (RL16_DEIRA) -  50S ribosomal protein L16
Seq:
Struc:
141 a.a.
124 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSJ5  (RL17_DEIRA) -  50S ribosomal protein L17
Seq:
Struc:
116 a.a.
114 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSL2  (RL18_DEIRA) -  50S ribosomal protein L18
Seq:
Struc:
114 a.a.
111 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RWB4  (RL19_DEIRA) -  50S ribosomal protein L19
Seq:
Struc:
166 a.a.
125 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSW7  (RL20_DEIRA) -  50S ribosomal protein L20
Seq:
Struc:
118 a.a.
117 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RY64  (RL21_DEIRA) -  50S ribosomal protein L21
Seq:
Struc:
100 a.a.
100 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXJ7  (RL22_DEIRA) -  50S ribosomal protein L22
Seq:
Struc:
134 a.a.
130 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXK0  (RL23_DEIRA) -  50S ribosomal protein L23
Seq:
Struc:
95 a.a.
93 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXJ1  (RL24_DEIRA) -  50S ribosomal protein L24
Seq:
Struc:
115 a.a.
113 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RX88  (RL25_DEIRA) -  50S ribosomal protein L25
Seq:
Struc:
237 a.a.
223 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RY65  (RL27_DEIRA) -  50S ribosomal protein L27
Seq:
Struc:
91 a.a.
86 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXJ4  (RL29_DEIRA) -  50S ribosomal protein L29
Seq:
Struc:
67 a.a.
65 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSL0  (RL30_DEIRA) -  50S ribosomal protein L30
Seq:
Struc:
55 a.a.
55 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RW44  (RL31_DEIRA) -  50S ribosomal protein L31
Seq:
Struc:
73 a.a.
73 a.a.
Protein chain
Pfam   ArchSchema ?
P49228  (RL32_DEIRA) -  50S ribosomal protein L32
Seq:
Struc:
60 a.a.
58 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSS4  (RL33_DEIRA) -  50S ribosomal protein L33
Seq:
Struc:
55 a.a.
53 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSH2  (RL34_DEIRA) -  50S ribosomal protein L34
Seq:
Struc:
47 a.a.
46 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSW6  (RL35_DEIRA) -  50S ribosomal protein L35
Seq:
Struc:
66 a.a.
63 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSK0  (RL36_DEIRA) -  50S ribosomal protein L36
Seq:
Struc:
37 a.a.
35 a.a.
Key:    PfamA domain  Secondary structure

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   4 terms 
  Biological process     translation   1 term 
  Biochemical function     structural constituent of ribosome     9 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(03)00022-4 Structure 11:329-338 (2003)
PubMed id: 12623020  
 
 
Structural basis for the antibiotic activity of ketolides and azalides.
F.Schlünzen, J.M.Harms, F.Franceschi, H.A.Hansen, H.Bartels, R.Zarivach, A.Yonath.
 
  ABSTRACT  
 
The azalide azithromycin and the ketolide ABT-773, which were derived by chemical modifications of erythromycin, exhibit elevated activity against a number of penicillin- and macrolide-resistant pathogenic bacteria. Analysis of the crystal structures of the large ribosomal subunit from Deinococcus radiodurans complexed with azithromycin or ABT-773 indicates that, despite differences in the number and nature of their contacts with the ribosome, both compounds exert their antimicrobial activity by blocking the protein exit tunnel. In contrast to all macrolides studied so far, two molecules of azithromycin bind simultaneously to the tunnel. The additional molecule also interacts with two proteins, L4 and L22, implicated in macrolide resistance. These studies illuminated and rationalized the enhanced activity of the drugs against specific macrolide-resistant bacteria.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Chemical Structures of ABT-773 and AzithromycinABT-773, left; azithromycin, right.
 
  The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 329-338) copyright 2003.  
  Figure was selected by an automated process.  

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.  
21245870 L.Zhang, B.Jiao, X.Yang, L.Liu, and S.Ma (2011).
Synthesis and antibacterial activity of new 4″-O-carbamates of 11,12-cyclic carbonate erythromycin A 6,9-imino ether.
  J Antibiot (Tokyo), 64, 243-247.  
20855725 B.Llano-Sotelo, J.Dunkle, D.Klepacki, W.Zhang, P.Fernandes, J.H.Cate, and A.S.Mankin (2010).
Binding and action of CEM-101, a new fluoroketolide antibiotic that inhibits protein synthesis.
  Antimicrob Agents Chemother, 54, 4961-4970.
PDB codes: 1vt2 3or9 3ora 3orb
20876130 D.Bulkley, C.A.Innis, G.Blaha, and T.A.Steitz (2010).
Revisiting the structures of several antibiotics bound to the bacterial ribosome.
  Proc Natl Acad Sci U S A, 107, 17158-17163.
PDB codes: 3oge 3ogy 3oh5 3oh7 3ohc 3ohd 3ohj 3ohk 3ohy 3ohz 3oi0 3oi1 3oi2 3oi3 3oi4 3oi5
20053150 G.Devasahayam, W.M.Scheld, and P.S.Hoffman (2010).
Newer antibacterial drugs for a new century.
  Expert Opin Investig Drugs, 19, 215-234.  
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.  
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
19929179 D.N.Wilson (2009).
The A-Z of bacterial translation inhibitors.
  Crit Rev Biochem Mol Biol, 44, 393-433.  
19164155 E.C.Kouvela, D.L.Kalpaxis, D.N.Wilson, and G.P.Dinos (2009).
Distinct mode of interaction of a novel ketolide antibiotic that displays enhanced antimicrobial activity.
  Antimicrob Agents Chemother, 53, 1411-1419.  
19150357 E.J.Diner, and C.S.Hayes (2009).
Recombineering reveals a diverse collection of ribosomal proteins L4 and L22 that confer resistance to macrolide antibiotics.
  J Mol Biol, 386, 300-315.  
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
19469554 G.Y.Soung, J.L.Miller, H.Koc, and E.C.Koc (2009).
Comprehensive analysis of phosphorylated proteins of Escherichia coli ribosomes.
  J Proteome Res, 8, 3390-3402.  
19779460 S.Chiba, A.Lamsa, and K.Pogliano (2009).
A ribosome-nascent chain sensor of membrane protein biogenesis in Bacillus subtilis.
  EMBO J, 28, 3461-3475.  
18804176 A.S.Mankin (2008).
Macrolide myths.
  Curr Opin Microbiol, 11, 414-421.  
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.  
18707551 M.Dongya, X.Wencheng, M.Xiaobo, and W.Lu (2008).
Transition mutations in 23S rRNA account for acquired resistance to macrolides in Ureaplasma urealyticum.
  Microb Drug Resist, 14, 183-186.  
18321237 M.R.Hammerschlag, and R.Sharma (2008).
Use of cethromycin, a new ketolide, for treatment of community-acquired respiratory infections.
  Expert Opin Investig Drugs, 17, 387-400.  
18439898 N.Vazquez-Laslop, C.Thum, and A.S.Mankin (2008).
Molecular mechanism of drug-dependent ribosome stalling.
  Mol Cell, 30, 190-202.  
19087267 R.M.Chico, R.Pittrof, B.Greenwood, and D.Chandramohan (2008).
Azithromycin-chloroquine and the intermittent preventive treatment of malaria in pregnancy.
  Malar J, 7, 255.  
17110371 A.B.Sidhu, Q.Sun, L.J.Nkrumah, M.W.Dunne, J.C.Sacchettini, and D.A.Fidock (2007).
In vitro efficacy, resistance selection, and structural modeling studies implicate the malarial parasite apicoplast as the target of azithromycin.
  J Biol Chem, 282, 2494-2504.  
17262863 C.Zhang, Q.Fu, C.Albermann, L.Li, and J.S.Thorson (2007).
The in vitro characterization of the erythronolide mycarosyltransferase EryBV and its utility in macrolide diversification.
  Chembiochem, 8, 385-390.  
17630700 E.S.Burgie, and H.M.Holden (2007).
Molecular architecture of DesI: a key enzyme in the biosynthesis of desosamine.
  Biochemistry, 46, 8999-9006.
PDB code: 2po3
18041896 F.Franceschi (2007).
Back to the future: the ribosome as an antibiotic target.
  Future Microbiol, 2, 571-574.  
17476984 G.A.Korshunova, N.V.Sumbatian, N.V.Fedorova, I.V.Kuznetsova, A.V.Shishkina, and A.A.Bogdanov (2007).
[Peptide derivatives of tylosin-related macrolides]
  Bioorg Khim, 33, 235-244.  
17169991 H.R.Jonker, S.Ilin, S.K.Grimm, J.Wöhnert, and H.Schwalbe (2007).
L11 domain rearrangement upon binding to RNA and thiostrepton studied by NMR spectroscopy.
  Nucleic Acids Res, 35, 441-454.
PDB codes: 2jq7 2nyo
17321546 S.J.Schroeder, G.Blaha, J.Tirado-Rives, T.A.Steitz, and P.B.Moore (2007).
The structures of antibiotics bound to the E site region of the 50 S ribosomal subunit of Haloarcula marismortui: 13-deoxytedanolide and girodazole.
  J Mol Biol, 367, 1471-1479.
PDB codes: 2otj 2otl
16825192 D.H.Sherman, S.Li, L.V.Yermalitskaya, Y.Kim, J.A.Smith, M.R.Waterman, and L.M.Podust (2006).
The structural basis for substrate anchoring, active site selectivity, and product formation by P450 PikC from Streptomyces venezuelae.
  J Biol Chem, 281, 26289-26297.
PDB codes: 2bvj 2c6h 2c7x 2cd8
16699167 L.Brandi, A.Fabbretti, M.Di Stefano, A.Lazzarini, M.Abbondi, and C.O.Gualerzi (2006).
Characterization of GE82832, a peptide inhibitor of translocation interacting with bacterial 30S ribosomal subunits.
  RNA, 12, 1262-1270.  
16923950 R.Berisio, N.Corti, P.Pfister, A.Yonath, and E.C.Böttger (2006).
23S rRNA 2058A-->G alteration mediates ketolide resistance in combination with deletion in L22.
  Antimicrob Agents Chemother, 50, 3816-3823.  
16538696 S.A.Borisova, C.Zhang, H.Takahashi, H.Zhang, A.W.Wong, J.S.Thorson, and H.W.Liu (2006).
Substrate specificity of the macrolide-glycosylating enzyme pair DesVII/DesVIII: opportunities, limitations, and mechanistic hypotheses.
  Angew Chem Int Ed Engl, 45, 2748-2753.  
16553874 T.Tenson, and A.Mankin (2006).
Antibiotics and the ribosome.
  Mol Microbiol, 59, 1664-1677.  
16180279 A.Yonath (2005).
Antibiotics targeting ribosomes: resistance, selectivity, synergism and cellular regulation.
  Annu Rev Biochem, 74, 649-679.  
16336118 D.N.Wilson, J.M.Harms, K.H.Nierhaus, F.Schlünzen, and P.Fucini (2005).
Species-specific antibiotic-ribosome interactions: implications for drug development.
  Biol Chem, 386, 1239-1252.  
16111914 J.A.Sutcliffe (2005).
Improving on nature: antibiotics that target the ribosome.
  Curr Opin Microbiol, 8, 534-542.  
15980485 J.Kleinjung, and F.Fraternali (2005).
POPSCOMP: an automated interaction analysis of biomolecular complexes.
  Nucleic Acids Res, 33, W342-W346.  
16261170 J.Poehlsgaard, and S.Douthwaite (2005).
The bacterial ribosome as a target for antibiotics.
  Nat Rev Microbiol, 3, 870-881.  
15897324 M.A.Xaplanteri, A.D.Petropoulos, G.P.Dinos, and D.L.Kalpaxis (2005).
Localization of spermine binding sites in 23S rRNA by photoaffinity labeling: parsing the spermine contribution to ribosomal 50S subunit functions.
  Nucleic Acids Res, 33, 2792-2805.  
16257828 N.Polacek, and A.S.Mankin (2005).
The ribosomal peptidyl transferase center: structure, function, evolution, inhibition.
  Crit Rev Biochem Mol Biol, 40, 285-311.  
15895524 S.J.Shaw, D.Abbanat, G.W.Ashley, K.Bush, B.Foleno, M.Macielag, D.Zhang, and D.C.Myles (2005).
15-amido erythromycins: synthesis and in vitro activity of a new class of macrolide antibiotics.
  J Antibiot (Tokyo), 58, 167-177.  
15919197 T.Hermann (2005).
Drugs targeting the ribosome.
  Curr Opin Struct Biol, 15, 355-366.  
16140535 T.Nomura, T.Iwaki, T.Yasukata, K.Nishi, Y.Narukawa, K.Uotani, T.Hori, and H.Miwa (2005).
A new type of ketolides bearing an N-aryl-alkyl acetamide moiety at the C-9 iminoether synthesis and structure-activity relationships.
  Bioorg Med Chem, 13, 6615-6628.  
15487937 A.Yonath, and A.Bashan (2004).
Ribosomal crystallography: initiation, peptide bond formation, and amino acid polymerization are hampered by antibiotics.
  Annu Rev Microbiol, 58, 233-251.  
15489173 C.D.Reeves, S.L.Ward, W.P.Revill, H.Suzuki, M.Marcus, O.V.Petrakovsky, S.Marquez, H.Fu, S.D.Dong, and L.Katz (2004).
Production of hybrid 16-membered macrolides by expressing combinations of polyketide synthase genes in engineered Streptomyces fradiae hosts.
  Chem Biol, 11, 1465-1472.  
15554968 F.Schlünzen, E.Pyetan, P.Fucini, A.Yonath, and J.M.Harms (2004).
Inhibition of peptide bond formation by pleuromutilins: the structure of the 50S ribosomal subunit from Deinococcus radiodurans in complex with tiamulin.
  Mol Microbiol, 54, 1287-1294.
PDB code: 1xbp
15059283 J.M.Harms, F.Schlünzen, P.Fucini, H.Bartels, and A.Yonath (2004).
Alterations at the peptidyl transferase centre of the ribosome induced by the synergistic action of the streptogramins dalfopristin and quinupristin.
  BMC Biol, 2, 4.
PDB code: 1sm1
15561874 J.Thompson, C.A.Pratt, and A.E.Dahlberg (2004).
Effects of a number of classes of 50S inhibitors on stop codon readthrough during protein synthesis.
  Antimicrob Agents Chemother, 48, 4889-4891.  
15385552 M.Lovmar, T.Tenson, and M.Ehrenberg (2004).
Kinetics of macrolide action: the josamycin and erythromycin cases.
  J Biol Chem, 279, 53506-53515.  
15491801 T.Auerbach, A.Bashan, and A.Yonath (2004).
Ribosomal antibiotics: structural basis for resistance, synergism and selectivity.
  Trends Biotechnol, 22, 570-576.  
15469510 V.Vimberg, L.Xiong, M.Bailey, T.Tenson, and A.Mankin (2004).
Peptide-mediated macrolide resistance reveals possible specific interactions in the nascent peptide exit tunnel.
  Mol Microbiol, 54, 376-385.  
15337844 Z.Druzina, and B.S.Cooperman (2004).
Photolabile anticodon stem-loop analogs of tRNAPhe as probes of ribosomal structure and structural fluctuation at the decoding center.
  RNA, 10, 1550-1562.  
12925991 A.Bashan, R.Zarivach, F.Schluenzen, I.Agmon, J.Harms, T.Auerbach, D.Baram, R.Berisio, H.Bartels, H.A.Hansen, P.Fucini, D.Wilson, M.Peretz, M.Kessler, and A.Yonath (2003).
Ribosomal crystallography: peptide bond formation and its inhibition.
  Biopolymers, 70, 19-41.  
14669983 A.Yonath (2003).
Ribosomal tolerance and peptide bond formation.
  Biol Chem, 384, 1411-1419.  
14523918 A.Yonath (2003).
Structural insight into functional aspects of ribosomal RNA targeting.
  Chembiochem, 4, 1008-1017.  
14661991 G.G.Zhanel, T.Hisanaga, K.Nichol, A.Wierzbowski, and D.J.Hoban (2003).
Ketolides: an emerging treatment for macrolide-resistant respiratory infections, focusing on S. pneumoniae.
  Expert Opin Emerg Drugs, 8, 297-321.  
12787020 I.Agmon, T.Auerbach, D.Baram, H.Bartels, A.Bashan, R.Berisio, P.Fucini, H.A.Hansen, J.Harms, M.Kessler, M.Peretz, F.Schluenzen, A.Yonath, and R.Zarivach (2003).
On peptide bond formation, translocation, nascent protein progression and the regulatory properties of ribosomes. Derived on 20 October 2002 at the 28th FEBS Meeting in Istanbul.
  Eur J Biochem, 270, 2543-2556.  
12665853 R.Berisio, F.Schluenzen, J.Harms, A.Bashan, T.Auerbach, D.Baram, and A.Yonath (2003).
Structural insight into the role of the ribosomal tunnel in cellular regulation.
  Nat Struct Biol, 10, 366-370.
PDB code: 1ond
12837804 R.Berisio, J.Harms, F.Schluenzen, R.Zarivach, H.A.Hansen, P.Fucini, and A.Yonath (2003).
Structural insight into the antibiotic action of telithromycin against resistant mutants.
  J Bacteriol, 185, 4276-4279.
PDB code: 1p9x
14523917 Y.Tor (2003).
Targeting RNA with small molecules.
  Chembiochem, 4, 998.  
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 codes are shown on the right.