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PDBsum entry 1yi2
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protein dna_rna ligands metals Protein-protein interface(s) links
Ribosome PDB id
1yi2

 

 

 

 

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Contents
Protein chains
237 a.a. *
337 a.a. *
246 a.a. *
140 a.a. *
172 a.a. *
119 a.a. *
29 a.a. *
160 a.a. *
70 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
ERY
Metals
_CL ×22
_NA ×86
_MG ×116
_CD ×5
__K ×2
Waters ×7808
* Residue conservation analysis
PDB id:
1yi2
Name: Ribosome
Title: Crystal structure of erythromycin bound to the g2099a mutant 50s ribosomal subunit of haloarcula marismortui
Structure: 23s ribosomal RNA. Chain: 0. Mutation: yes. Other_details: encoded by rrna operon. 5s ribosomal RNA. Chain: 9. 50s ribosomal protein l2p. Chain: a. 50s ribosomal protein l3p.
Source: Haloarcula marismortui. Organism_taxid: 2238. Strain: dt38. Strain: dt38
Biol. unit: 31mer (from PQS)
Resolution:
2.65Å     R-factor:   0.176     R-free:   0.214
Authors: D.Tu,G.Blaha,P.B.Moore,T.A.Steitz
Key ref:
D.Tu et al. (2005). Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide a structural explanation for resistance. Cell, 121, 257-270. PubMed id: 15851032 DOI: 10.1016/j.cell.2005.02.005
Date:
11-Jan-05     Release date:   26-Apr-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P20276  (RL2_HALMA) -  Large ribosomal subunit protein uL2 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		240 a.a.
237 a.a.
Protein chain
Pfam   ArchSchema ?
P20279  (RL3_HALMA) -  Large ribosomal subunit protein uL3 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		338 a.a.
337 a.a.
Protein chain
Pfam   ArchSchema ?
P12735  (RL4_HALMA) -  Large ribosomal subunit protein uL4 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		246 a.a.
246 a.a.*
Protein chain
Pfam   ArchSchema ?
P14124  (RL5_HALMA) -  Large ribosomal subunit protein uL5 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		177 a.a.
140 a.a.
Protein chain
Pfam   ArchSchema ?
P14135  (RL6_HALMA) -  Large ribosomal subunit protein uL6 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		178 a.a.
172 a.a.
Protein chain
Pfam   ArchSchema ?
P12743  (RL7A_HALMA) -  Large ribosomal subunit protein eL8 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		120 a.a.
119 a.a.
Protein chain
Pfam   ArchSchema ?
P15825  (RL10_HALMA) -  Large ribosomal subunit protein uL10 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		348 a.a.
29 a.a.*
Protein chain
Pfam   ArchSchema ?
P60617  (RL10E_HALMA) -  Large ribosomal subunit protein uL16 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		177 a.a.
160 a.a.
Protein chain
Pfam   ArchSchema ?
P14122  (RL11_HALMA) -  Large ribosomal subunit protein uL11 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		162 a.a.
70 a.a.
Protein chain
Pfam   ArchSchema ?
P29198  (RL13_HALMA) -  Large ribosomal subunit protein uL13 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		145 a.a.
142 a.a.
Protein chain
Pfam   ArchSchema ?
P22450  (RL14_HALMA) -  Large ribosomal subunit protein uL14 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		132 a.a.
132 a.a.*
Protein chain
Pfam   ArchSchema ?
P12737  (RL15_HALMA) -  Large ribosomal subunit protein uL15 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		165 a.a.
145 a.a.
Protein chain
Pfam   ArchSchema ?
P60618  (RL15E_HALMA) -  Large ribosomal subunit protein eL15 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		196 a.a.
194 a.a.*
Protein chain
Pfam   ArchSchema ?
P14123  (RL18_HALMA) -  Large ribosomal subunit protein uL18 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		187 a.a.
186 a.a.
Protein chain
Pfam   ArchSchema ?
P12733  (RL18E_HALMA) -  Large ribosomal subunit protein eL18 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		116 a.a.
115 a.a.
Protein chain
Pfam   ArchSchema ?
P14119  (RL19E_HALMA) -  Large ribosomal subunit protein eL19 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		149 a.a.
143 a.a.
Protein chain
Pfam   ArchSchema ?
P12734  (RL21_HALMA) -  Large ribosomal subunit protein eL21 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		96 a.a.
95 a.a.
Protein chain
Pfam   ArchSchema ?
P10970  (RL22_HALMA) -  Large ribosomal subunit protein uL22 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		155 a.a.
150 a.a.
Protein chain
Pfam   ArchSchema ?
P12732  (RL23_HALMA) -  Large ribosomal subunit protein uL23 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		85 a.a.
81 a.a.
Protein chain
Pfam   ArchSchema ?
P10972  (RL24_HALMA) -  Large ribosomal subunit protein uL24 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		120 a.a.
119 a.a.
Protein chain
Pfam   ArchSchema ?
P14116  (RL24E_HALMA) -  Large ribosomal subunit protein eL24 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		67 a.a.
53 a.a.
Protein chain
Pfam   ArchSchema ?
P10971  (RL29_HALMA) -  Large ribosomal subunit protein uL29 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		71 a.a.
65 a.a.
Protein chain
Pfam   ArchSchema ?
P14121  (RL30_HALMA) -  Large ribosomal subunit protein uL30 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		154 a.a.
154 a.a.
Protein chain
Pfam   ArchSchema ?
P18138  (RL31_HALMA) -  Large ribosomal subunit protein eL31 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		92 a.a.
82 a.a.
Protein chain
Pfam   ArchSchema ?
P12736  (RL32_HALMA) -  Large ribosomal subunit protein eL32 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		241 a.a.
142 a.a.
Protein chain
Pfam   ArchSchema ?
P60619  (RL37A_HALMA) -  Large ribosomal subunit protein eL43 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		92 a.a.
73 a.a.*
Protein chain
Pfam   ArchSchema ?
P32410  (RL37_HALMA) -  Large ribosomal subunit protein eL37 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		57 a.a.
56 a.a.
Protein chain
Pfam   ArchSchema ?
P22452  (RL39_HALMA) -  Large ribosomal subunit protein eL39 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		50 a.a.
46 a.a.
Protein chain
Pfam   ArchSchema ?
P32411  (RL44E_HALMA) -  Large ribosomal subunit protein eL42 from Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
Seq:
Struc: 		92 a.a.
92 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 15 residue positions (black crosses)

DNA/RNA chains
  U-A-U-G-C-C-A-G-C-U-G-G-U-G-G-A-U-U-G-C-U-C-G-G-C-U-C-A-G-G-C-G-C-U-G-A-U-G-A- ... 2754 bases
  U-U-A-G-G-C-G-G-C-C-A-C-A-G-C-G-G-U-G-G-G-G-U-U-G-C-C-U-C-C-C-G-U-A-C-C-C-A-U- 122 bases

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q, R, S, T, U, V, W, X, Y, Z, 1, 2, 3: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1016/j.cell.2005.02.005 Cell 121:257-270 (2005)
PubMed id: 15851032  
 
 
Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide a structural explanation for resistance.
D.Tu, G.Blaha, P.B.Moore, T.A.Steitz.
 
  ABSTRACT  
 
Crystal structures of H. marismortui large ribosomal subunits containing the mutation G2099A (A2058 in E. coli) with erythromycin, azithromycin, clindamycin, virginiamycin S, and telithromycin bound explain why eubacterial ribosomes containing the mutation A2058G are resistant to them. Azithromycin binds almost identically to both G2099A and wild-type subunits, but the erythromycin affinity increases by more than 10(4)-fold, implying that desolvation of the N2 of G2099 accounts for the low wild-type affinity for macrolides. All macrolides bind similarly to the H. marismortui subunit, but their binding differs significantly from what has been reported in the D. radioidurans subunit. The synergy in the binding of streptogramins A and B appears to result from a reorientation of the base of A2103 (A2062, E. coli) that stacks between them. The structure of large subunit containing a three residue deletion mutant of L22 shows a change in the L22 structure and exit tunnel shape that illuminates its macrolide resistance phenotype.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. A Model of the Eight N-Terminal Amino Acids of the ermC Operon Leader Peptide Bound at the PTC End of the Peptide Exit Tunnel 		Figure 6.
Figure 6. Differences between Models of MLS[B]K Antibiotics Bound to the H. marismortui (Hma) and D. radiodurans (Dra) Ribosomes
 
  The above figures are reprinted by permission from Cell Press: Cell (2005, 121, 257-270) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22664983 S.Melnikov, A.Ben-Shem, N.Garreau de Loubresse, L.Jenner, G.Yusupova, and M.Yusupov (2012).
One core, two shells: bacterial and eukaryotic ribosomes.
  Nat Struct Mol Biol, 19, 560-567.  
21292164 H.Ramu, N.Vázquez-Laslop, D.Klepacki, Q.Dai, J.Piccirilli, R.Micura, and A.S.Mankin (2011).
Nascent peptide in the ribosome exit tunnel affects functional properties of the A-site of the peptidyl transferase center.
  Mol Cell, 41, 321-330.  
21282615 M.J.Belousoff, T.Shapira, A.Bashan, E.Zimmerman, H.Rozenberg, K.Arakawa, H.Kinashi, and A.Yonath (2011).
Crystal structure of the synergistic antibiotic pair, lankamycin and lankacidin, in complex with the large ribosomal subunit.
  Proc Natl Acad Sci U S A, 108, 2717-2722.
PDB codes: 3pio 3pip
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.  
19940122 A.I.Guce, N.E.Clark, E.N.Salgado, D.R.Ivanen, A.A.Kulminskaya, H.Brumer, and S.C.Garman (2010).
Catalytic mechanism of human alpha-galactosidase.
  J Biol Chem, 285, 3625-3632.
PDB codes: 3hg2 3hg3 3hg4 3hg5
20534348 A.L.Starosta, V.V.Karpenko, A.V.Shishkina, A.Mikolajka, N.V.Sumbatyan, F.Schluenzen, G.A.Korshunova, A.A.Bogdanov, and D.N.Wilson (2010).
Interplay between the ribosomal tunnel, nascent chain, and macrolides influences drug inhibition.
  Chem Biol, 17, 504-514.  
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
20121095 C.T.Walsh, and M.A.Fischbach (2010).
Natural products version 2.0: connecting genes to molecules.
  J Am Chem Soc, 132, 2469-2493.  
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
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
20841923 J.J.Holstein, P.Luger, R.Kalinowski, S.Mebs, C.Paulman, and B.Dittrich (2010).
Validation of experimental charge densities: refinement of the macrolide antibiotic roxithromycin.
  Acta Crystallogr B, 66, 568-577.  
20124689 K.Ravikumar, and B.Sridhar (2010).
Clindamycin hydrochloride monohydrate and its ethanol solvate.
  Acta Crystallogr C, 66, o97-100.  
20822442 M.Morar, and G.D.Wright (2010).
The genomic enzymology of antibiotic resistance.
  Annu Rev Genet, 44, 25-51.  
20676057 N.Vázquez-Laslop, H.Ramu, D.Klepacki, K.Kannan, and A.S.Mankin (2010).
The key function of a conserved and modified rRNA residue in the ribosomal response to the nascent peptide.
  EMBO J, 29, 3108-3117.  
20876111 S.Douthwaite (2010).
Designer drugs for discerning bugs.
  Proc Natl Acad Sci U S A, 107, 17065-17066.  
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
20154667 T.Schneider-Poetsch, T.Usui, D.Kaida, and M.Yoshida (2010).
Garbled messages and corrupted translations.
  Nat Chem Biol, 6, 189-198.  
20698993 U.Allas, and T.Tenson (2010).
A method for selecting cis-acting regulatory sequences that respond to small molecule effectors.
  BMC Mol Biol, 11, 56.  
19270700 A.Kosolapov, and C.Deutsch (2009).
Tertiary interactions within the ribosomal exit tunnel.
  Nat Struct Mol Biol, 16, 405-411.  
19875082 A.L.Starosta, H.Qin, A.Mikolajka, G.Y.Leung, K.Schwinghammer, K.C.Nicolaou, D.Y.Chen, B.S.Cooperman, and D.N.Wilson (2009).
Identification of distinct thiopeptide-antibiotic precursor lead compounds using translation machinery assays.
  Chem Biol, 16, 1087-1096.  
19656820 A.Yonath (2009).
Large facilities and the evolving ribosome, the cellular machine for genetic-code translation.
  J R Soc Interface, 6, S575-S585.  
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.  
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.  
20004157 J.A.Sundlov, and A.M.Gulick (2009).
Insights into resistance against lincosamide antibiotics.
  Structure, 17, 1549-1550.  
19002604 J.J.Headd, R.M.Immormino, D.A.Keedy, P.Emsley, D.C.Richardson, and J.S.Richardson (2009).
Autofix for backward-fit sidechains: using MolProbity and real-space refinement to put misfits in their place.
  J Struct Funct Genomics, 10, 83-93.  
19197244 M.Lovmar, K.Nilsson, E.Lukk, V.Vimberg, T.Tenson, and M.Ehrenberg (2009).
Erythromycin resistance by L4/L22 mutations and resistance masking by drug efflux pump deficiency.
  EMBO J, 28, 736-744.  
20004168 M.Morar, K.Bhullar, D.W.Hughes, M.Junop, and G.D.Wright (2009).
Structure and mechanism of the lincosamide antibiotic adenylyltransferase LinB.
  Structure, 17, 1649-1659.
PDB codes: 3jyy 3jz0
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.  
19029332 T.Siibak, L.Peil, L.Xiong, A.Mankin, J.Remme, and T.Tenson (2009).
Erythromycin- and chloramphenicol-induced ribosomal assembly defects are secondary effects of protein synthesis inhibition.
  Antimicrob Agents Chemother, 53, 563-571.  
19486296 T.Tenson, and V.Hauryliuk (2009).
Does the ribosome have initiation and elongation modes of translation?
  Mol Microbiol, 72, 1310-1315.  
18079110 A.D.Petropoulos, E.C.Kouvela, G.P.Dinos, and D.L.Kalpaxis (2008).
Stepwise binding of tylosin and erythromycin to Escherichia coli ribosomes, characterized by kinetic and footprinting analysis.
  J Biol Chem, 283, 4756-4765.  
18218702 A.S.Bommakanti, L.Lindahl, and J.M.Zengel (2008).
Mutation from guanine to adenine in 25S rRNA at the position equivalent to E. coli A2058 does not confer erythromycin sensitivity in Sacchromyces cerevisae.
  RNA, 14, 460-464.  
18804176 A.S.Mankin (2008).
Macrolide myths.
  Curr Opin Microbiol, 11, 414-421.  
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.  
18247347 C.H.Lu, S.W.Huang, Y.L.Lai, C.P.Lin, C.H.Shih, C.C.Huang, W.L.Hsu, and J.K.Hwang (2008).
On the relationship between the protein structure and protein dynamics.
  Proteins, 72, 625-634.  
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
18195060 D.R.Gentry, and D.J.Holmes (2008).
Selection for high-level telithromycin resistance in Staphylococcus aureus yields mutants resulting from an rplB-to-rplV gene conversion-like event.
  Antimicrob Agents Chemother, 52, 1156-1158.  
18201149 F.Van Bambeke, J.M.Harms, Y.Van Laethem, and P.M.Tulkens (2008).
Ketolides: pharmacological profile and rational positioning in the treatment of respiratory tract infections.
  Expert Opin Pharmacother, 9, 267-283.  
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.  
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.  
18086834 M.Bailey, T.Chettiath, and A.S.Mankin (2008).
Induction of erm(C) expression by noninducing antibiotics.
  Antimicrob Agents Chemother, 52, 866-874.  
18399991 M.C.Roberts (2008).
Update on macrolide-lincosamide-streptogramin, ketolide, and oxazolidinone resistance genes.
  FEMS Microbiol Lett, 282, 147-159.  
18586934 M.G.Lawrence, L.Lindahl, and J.M.Zengel (2008).
Effects on translation pausing of alterations in protein and RNA components of the ribosome exit tunnel.
  J Bacteriol, 190, 5862-5869.  
18439898 N.Vazquez-Laslop, C.Thum, and A.S.Mankin (2008).
Molecular mechanism of drug-dependent ribosome stalling.
  Mol Cell, 30, 190-202.  
18056269 N.Wolter, A.M.Smith, D.J.Farrell, J.B.Northwood, S.Douthwaite, and K.P.Klugman (2008).
Telithromycin Resistance in Streptococcus pneumoniae Is Conferred by a Deletion in the Leader Sequence of erm(B) That Increases rRNA Methylation.
  Antimicrob Agents Chemother, 52, 435-440.  
19015512 S.D.Moore, and R.T.Sauer (2008).
Revisiting the mechanism of macrolide-antibiotic resistance mediated by ribosomal protein L22.
  Proc Natl Acad Sci U S A, 105, 18261-18266.  
18025251 S.M.Toh, L.Xiong, T.Bae, and A.S.Mankin (2008).
The methyltransferase YfgB/RlmN is responsible for modification of adenosine 2503 in 23S rRNA.
  RNA, 14, 98.  
18382121 T.A.Steitz (2008).
Structural insights into the functions of the large ribosomal subunit, a major antibiotic target.
  Keio J Med, 57, 1.  
18802638 U.Schell, S.F.Haydock, A.L.Kaja, I.Carletti, R.E.Lill, E.Read, L.S.Sheehan, L.Low, M.J.Fernandez, F.Grolle, H.A.McArthur, R.M.Sheridan, P.F.Leadlay, B.Wilkinson, and S.Gaisser (2008).
Engineered biosynthesis of hybrid macrolide polyketides containing D-angolosamine and D-mycaminose moieties.
  Org Biomol Chem, 6, 3315-3327.  
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.  
17591769 A.Yassin, and A.S.Mankin (2007).
Potential new antibiotic sites in the ribosome revealed by deleterious mutations in RNA of the large ribosomal subunit.
  J Biol Chem, 282, 24329-24342.  
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.  
17376874 D.N.Bolam, S.Roberts, M.R.Proctor, J.P.Turkenburg, E.J.Dodson, C.Martinez-Fleites, M.Yang, B.G.Davis, G.J.Davies, and H.J.Gilbert (2007).
The crystal structure of two macrolide glycosyltransferases provides a blueprint for host cell antibiotic immunity.
  Proc Natl Acad Sci U S A, 104, 5336-5341.
PDB codes: 2iya 2iyf
18041896 F.Franceschi (2007).
Back to the future: the ribosome as an antibiotic target.
  Future Microbiol, 2, 571-574.  
17298179 H.Y.Lee, and C.Khosla (2007).
Bioassay-guided evolution of glycosylated macrolide antibiotics in Escherichia coli.
  PLoS Biol, 5, e45.  
17159922 L.L.Silver (2007).
Multi-targeting by monotherapeutic antibacterials.
  Nat Rev Drug Discov, 6, 41-55.  
17563376 M.Korczynska, T.A.Mukhtar, G.D.Wright, and A.M.Berghuis (2007).
Structural basis for streptogramin B resistance in Staphylococcus aureus by virginiamycin B lyase.
  Proc Natl Acad Sci U S A, 104, 10388-10393.
PDB codes: 2z2n 2z2o 2z2p
17951392 M.Macvanin, E.I.Gonzalez de Valdivia, D.H.Ardell, and L.A.Isaksson (2007).
Transient erythromycin resistance phenotype associated with peptidyl-tRNA drop-off on early UGG and GGG codons.
  J Bacteriol, 189, 8993-9000.  
17908942 R.Binet, and A.T.Maurelli (2007).
Frequency of development and associated physiological cost of azithromycin resistance in Chlamydia psittaci 6BC and C. trachomatis L2.
  Antimicrob Agents Chemother, 51, 4267-4275.  
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
17555436 S.M.Toh, L.Xiong, C.A.Arias, M.V.Villegas, K.Lolans, J.Quinn, and A.S.Mankin (2007).
Acquisition of a natural resistance gene renders a clinical strain of methicillin-resistant Staphylococcus aureus resistant to the synthetic antibiotic linezolid.
  Mol Microbiol, 64, 1506-1514.  
17956547 S.Zaman, M.Fitzpatrick, L.Lindahl, and J.Zengel (2007).
Novel mutations in ribosomal proteins L4 and L22 that confer erythromycin resistance in Escherichia coli.
  Mol Microbiol, 66, 1039-1050.  
16337126 A.S.Mankin (2006).
Nascent peptide in the "birth canal" of the ribosome.
  Trends Biochem Sci, 31, 11-13.  
16940070 C.Cagliero, C.Mouline, A.Cloeckaert, and S.Payot (2006).
Synergy between efflux pump CmeABC and modifications in ribosomal proteins L4 and L22 in conferring macrolide resistance in Campylobacter jejuni and Campylobacter coli.
  Antimicrob Agents Chemother, 50, 3893-3896.  
16845429 D.H.Bunka, and P.G.Stockley (2006).
Aptamers come of age - at last.
  Nat Rev Microbiol, 4, 588-596.  
16490268 E.C.Böttger (2006).
The ribosome as a drug target.
  Trends Biotechnol, 24, 145-147.  
16760473 E.C.Kouvela, A.D.Petropoulos, and D.L.Kalpaxis (2006).
Unraveling new features of clindamycin interaction with functional ribosomes and dependence of the drug potency on polyamines.
  J Biol Chem, 281, 23103-23110.  
16773394 G.Papadopoulos, S.Grudinin, D.L.Kalpaxis, and T.Choli-Papadopoulou (2006).
Changes in the level of poly(Phe) synthesis in Escherichia coli ribosomes containing mutants of L4 ribosomal protein from Thermus thermophilus can be explained by structural changes in the peptidyltransferase center: a molecular dynamics simulation analysis.
  Eur Biophys J, 35, 675-683.  
17160060 J.Clardy, M.A.Fischbach, and C.T.Walsh (2006).
New antibiotics from bacterial natural products.
  Nat Biotechnol, 24, 1541-1550.  
16607023 K.L.Muldoon-Jacobs, and J.D.Dinman (2006).
Specific effects of ribosome-tethered molecular chaperones on programmed -1 ribosomal frameshifting.
  Eukaryot Cell, 5, 762-770.  
16801432 K.S.Long, J.Poehlsgaard, C.Kehrenberg, S.Schwarz, and B.Vester (2006).
The Cfr rRNA methyltransferase confers resistance to Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and Streptogramin A antibiotics.
  Antimicrob Agents Chemother, 50, 2500-2505.  
16410246 M.Lovmar, K.Nilsson, V.Vimberg, T.Tenson, M.Nervall, and M.Ehrenberg (2006).
The molecular mechanism of peptide-mediated erythromycin resistance.
  J Biol Chem, 281, 6742-6750.  
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.  
17014718 S.M.Halling, and A.E.Jensen (2006).
Intrinsic and selected resistance to antibiotics binding the ribosome: analyses of Brucella 23S rrn, L4, L22, EF-Tu1, EF-Tu2, efflux and phylogenetic implications.
  BMC Microbiol, 6, 84.  
16553874 T.Tenson, and A.Mankin (2006).
Antibiotics and the ribosome.
  Mol Microbiol, 59, 1664-1677.  
16091044 C.Kehrenberg, S.Schwarz, L.Jacobsen, L.H.Hansen, and B.Vester (2005).
A new mechanism for chloramphenicol, florfenicol and clindamycin resistance: methylation of 23S ribosomal RNA at A2503.
  Mol Microbiol, 57, 1064-1073.  
16174779 C.T.Madsen, L.Jakobsen, K.Buriánková, F.Doucet-Populaire, J.L.Pernodet, and S.Douthwaite (2005).
Methyltransferase Erm(37) slips on rRNA to confer atypical resistance in Mycobacterium tuberculosis.
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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.  
15970993 D.Tu, G.Blaha, P.B.Moore, and T.A.Steitz (2005).
Gene replacement in Haloarcula marismortui: construction of a strain with two of its three chromosomal rRNA operons deleted.
  Extremophiles, 9, 427-435.  
16111914 J.A.Sutcliffe (2005).
Improving on nature: antibiotics that target the ribosome.
  Curr Opin Microbiol, 8, 534-542.  
16261170 J.Poehlsgaard, and S.Douthwaite (2005).
The bacterial ribosome as a target for antibiotics.
  Nat Rev Microbiol, 3, 870-881.  
16253545 J.Soppa (2005).
From replication to cultivation: hot news from Haloarchaea.
  Curr Opin Microbiol, 8, 737-744.  
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.  
16194243 S.Douthwaite, J.Jalava, and L.Jakobsen (2005).
Ketolide resistance in Streptococcus pyogenes correlates with the degree of rRNA dimethylation by Erm.
  Mol Microbiol, 58, 613-622.  
15919197 T.Hermann (2005).
Drugs targeting the ribosome.
  Curr Opin Struct Biol, 15, 355-366.  
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.

 

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