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PDBsum entry 3ccl

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protein dna_rna metals Protein-protein interface(s) links
Ribosome PDB id
3ccl
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. *
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
Metals
_SR ×108
_NA ×75
_CL ×22
_MG ×93
_CD ×5
__K ×2
Waters ×7823
* Residue conservation analysis
PDB id:
3ccl
Name: Ribosome
Title: Structure of anisomycin resistant 50s ribosomal subunit: 23s mutation u2535c. Density for anisomycin is visible but not in model.
Structure: 50s ribosomal protein l2p. Chain: a. Synonym: hmal2, hl4. 50s ribosomal protein l3p. Chain: b. Synonym: hmal3, hl1. 50s ribosomal protein l4p. Chain: c. Synonym: hmal4, hl6.
Source: Haloarcula marismortui. Halobacterium marismortui. Halobacterium marismortui
Resolution:
2.90Å     R-factor:   0.171     R-free:   0.220
Authors: G.Blaha,G.Gurel
Key ref:
G.Blaha et al. (2008). Mutations outside the anisomycin-binding site can make ribosomes drug-resistant. J Mol Biol, 379, 505-519. PubMed id: 18455733 DOI: 10.1016/j.jmb.2008.03.075
Date:
26-Feb-08     Release date:   20-May-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P20276  (RL2_HALMA) -  50S ribosomal protein L2
Seq:
Struc:
240 a.a.
237 a.a.
Protein chain
Pfam   ArchSchema ?
P20279  (RL3_HALMA) -  50S ribosomal protein L3
Seq:
Struc:
338 a.a.
337 a.a.
Protein chain
Pfam   ArchSchema ?
P12735  (RL4_HALMA) -  50S ribosomal protein L4
Seq:
Struc:
246 a.a.
246 a.a.
Protein chain
Pfam   ArchSchema ?
P14124  (RL5_HALMA) -  50S ribosomal protein L5
Seq:
Struc:
177 a.a.
140 a.a.
Protein chain
Pfam   ArchSchema ?
P14135  (RL6_HALMA) -  50S ribosomal protein L6
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 L10
Seq:
Struc:
348 a.a.
29 a.a.*
Protein chain
Pfam   ArchSchema ?
P60617  (RL10_HALMA) -  50S ribosomal protein L10e
Seq:
Struc:
177 a.a.
160 a.a.
Protein chain
Pfam   ArchSchema ?
P14122  (RL11_HALMA) -  50S ribosomal protein L11
Seq:
Struc:
162 a.a.
70 a.a.
Protein chain
Pfam   ArchSchema ?
P29198  (RL13_HALMA) -  50S ribosomal protein L13
Seq:
Struc:
145 a.a.
142 a.a.
Protein chain
Pfam   ArchSchema ?
P22450  (RL14_HALMA) -  50S ribosomal protein L14
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 11 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   5 terms 
  Biological process     ribosome biogenesis   7 terms 
  Biochemical function     structural constituent of ribosome     11 terms  

 

 
DOI no: 10.1016/j.jmb.2008.03.075 J Mol Biol 379:505-519 (2008)
PubMed id: 18455733  
 
 
Mutations outside the anisomycin-binding site can make ribosomes drug-resistant.
G.Blaha, G.Gürel, S.J.Schroeder, P.B.Moore, T.A.Steitz.
 
  ABSTRACT  
 
Eleven mutations that make Haloarcula marismortui resistant to anisomycin, an antibiotic that competes with the amino acid side chains of aminoacyl tRNAs for binding to the A-site cleft of the large ribosomal unit, have been identified in 23S rRNA. The correlation observed between the sensitivity of H. marismortui to anisomycin and the affinity of its large ribosomal subunits for the drug indicates that its response to anisomycin is determined primarily by the binding of the drug to its large ribosomal subunit. The structures of large ribosomal subunits containing resistance mutations show that these mutations can be divided into two classes: (1) those that interfere with specific drug-ribosome interactions and (2) those that stabilize the apo conformation of the A-site cleft of the ribosome relative to its drug-bound conformation. The conformational effects of some mutations of the second kind propagate through the ribosome for considerable distances and are reversed when A-site substrates bind to the ribosome.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. A global view of the positions of the bases, the mutation of which cause anisomycin resistance in H. marismortui. The drug (gold with spherical atoms) is shown surrounded by the bases, the mutation of which leads to drug resistance (red). The backbone connecting the bases is indicated in gray. The positions occupied by the CCA end of P-site-bound tRNA (orange) and A-site-bound tRNA (green) are shown for orientation. E. coli numbering is used for all bases.
Figure 5.
Fig. 5. The effect of A-site substrate binding on the conformation of large ribosomal subunits containing the mutation G2581A. (a) Comparison of the conformation of the 2581 region of wild-type ribosomes (gray) with that of the G2581A mutant (green). Also included in the figure is CC-puromycin (blue green) as reference for the binding site of amino acylated tRNA to the A-site. (b) Comparison of the structure of G2581A mutant (green) and CC-puromycin bound to a large ribosomal subunit of wild type (gold). (c) Comparison of the structures of G2581A mutant (green) and of CC-puromycin bound to G2581A (khaki) with overlaid (F[G2581A]−F[G2581A CC-puromycin]) difference electron density, which was computed by using as amplitudes the differences observed between the data obtained from G2581A crystals that include the analog and the data obtained from G2581A crystals that lack the analog. Positive features were contoured at + 4σ (blue), and negative features were contoured at − 4σ (red).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 379, 505-519) copyright 2008.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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
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
20562215 K.T.Schroeder, S.A.McPhee, J.Ouellet, and D.M.Lilley (2010).
A structural database for k-turn motifs in RNA.
  RNA, 16, 1463-1468.  
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.  
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.  
  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
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.  
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.  
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.  
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
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.