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Contents |
 |
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237 a.a.
|
 |
|
|
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|
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206 a.a.
|
 |
|
|
|
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|
|
|
208 a.a.
|
 |
|
|
|
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150 a.a.
|
 |
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101 a.a.
|
 |
|
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155 a.a.
|
 |
|
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138 a.a.
|
 |
|
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127 a.a.
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98 a.a.
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119 a.a.
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 |
|
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125 a.a.
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 |
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125 a.a.
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 |
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60 a.a.
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88 a.a.
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 |
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83 a.a.
|
 |
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104 a.a.
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 |
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73 a.a.
|
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84 a.a.
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99 a.a.
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24 a.a.
|
 |
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* Residue conservation analysis
|
|
|
|
|
PDB id:
|
 |
|
 |
| Name: |
 |
Ribosome
|
 |
|
Title:
|
 |
Structure of the thermus thermophilus 30s ribosomal subunit in complex with the antibiotics streptomycin, spectinomycin, and paromomycin
|
|
Structure:
|
 |
16s ribosomal RNA. Chain: a. Fragment of messenger RNA. Chain: x. 30s ribosomal protein s2. Chain: b. 30s ribosomal protein s3. Chain: c. 30s ribosomal protein s4.
|
|
Source:
|
 |
Thermus thermophilus. Organism_taxid: 274. Organism_taxid: 274
|
|
Biol. unit:
|
 |
22mer (from
)
|
|
Resolution:
|
 |
|
3.00Å
|
R-factor:
|
0.221
|
R-free:
|
0.255
|
|
|
Authors:
|
 |
A.P.Carter,W.M.Clemons Jr.,D.E.Brodersen,B.T.Wimberly, R.J.Morgan-Warren,V.Ramakrishnan
|
Key ref:
|
 |
A.P.Carter
et al.
(2000).
Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics.
Nature,
407,
340-348.
PubMed id:
DOI:
|
 |
|
Date:
|
 |
|
08-Aug-00
|
Release date:
|
25-Sep-00
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
Headers
|
 |
|
|
References
|
|
|
|
|
|
|
P80371
(RS2_THET8) -
30S ribosomal protein S2
|
|
|
|
Seq: Struc:
|
 |
 |
 |
256 a.a.
237 a.a.
|
|
|
|
|
|
|
 |
 |
|
|
|
|
P80372
(RS3_THET8) -
30S ribosomal protein S3
|
|
|
|
Seq: Struc:
|
 |
 |
 |
239 a.a.
206 a.a.
|
|
|
|
|
|
|
 |
 |
|
|
|
|
P80373
(RS4_THET8) -
30S ribosomal protein S4
|
|
|
|
Seq: Struc:
|
 |
 |
 |
209 a.a.
208 a.a.*
|
|
|
|
|
|
|
 |
 |
|
|
|
|
Q5SHQ5
(RS5_THET8) -
30S ribosomal protein S5
|
|
|
|
Seq: Struc:
|
 |
 |
 |
162 a.a.
150 a.a.
|
|
|
|
|
|
|
 |
 |
|
|
|
|
Q5SLP8
(RS6_THET8) -
30S ribosomal protein S6
|
|
|
|
Seq: Struc:
|
 |
 |
 |
101 a.a.
101 a.a.
|
|
|
|
|
|
|
 |
 |
|
|
|
|
P17291
(RS7_THET8) -
30S ribosomal protein S7
|
|
|
|
Seq: Struc:
|
 |
 |
 |
156 a.a.
155 a.a.
|
|
|
|
|
|
|
 |
 |
|
|
|
|
Q5SHQ2
(RS8_THET8) -
30S ribosomal protein S8
|
|
|
|
Seq: Struc:
|
 |
 |
 |
138 a.a.
138 a.a.
|
|
|
|
|
|
|
 |
 |
|
|
|
|
P80374
(RS9_THET8) -
30S ribosomal protein S9
|
|
|
|
Seq: Struc:
|
 |
 |
 |
128 a.a.
127 a.a.*
|
|
|
|
|
|
|
 |
 |
|
|
|
|
Q5SHN7
(RS10_THET8) -
30S ribosomal protein S10
|
|
|
|
Seq: Struc:
|
 |
 |
 |
105 a.a.
98 a.a.
|
|
|
|
|
|
|
 |
 |
|
|
|
|
P80376
(RS11_THET8) -
30S ribosomal protein S11
|
|
|
|
Seq: Struc:
|
 |
 |
 |
129 a.a.
119 a.a.
|
|
|
|
|
|
|
 |
 |
|
|
|
|
Q5SHN3
(RS12_THET8) -
30S ribosomal protein S12
|
|
|
|
Seq: Struc:
|
 |
 |
 |
132 a.a.
125 a.a.
|
|
|
|
|
|
|
 |
 |
|
|
|
|
P80377
(RS13_THET8) -
30S ribosomal protein S13
|
|
|
|
Seq: Struc:
|
 |
 |
 |
126 a.a.
125 a.a.
|
|
|
|
|
|
|
 |
 |
|
|
|
|
Q5SHQ1
(RS14Z_THET8) -
30S ribosomal protein S14 type Z
|
|
|
|
Seq: Struc:
|
 |
 |
 |
61 a.a.
60 a.a.
|
|
|
|
|
|
|
 |
 |
|
|
|
|
Q5SJ76
(RS15_THET8) -
30S ribosomal protein S15
|
|
|
|
Seq: Struc:
|
 |
 |
 |
89 a.a.
88 a.a.
|
|
|
|
|
|
|
 |
 |
|
|
|
|
Q5SJH3
(RS16_THET8) -
30S ribosomal protein S16
|
|
|
|
Seq: Struc:
|
 |
 |
 |
88 a.a.
83 a.a.
|
|
|
|
|
|
|
 |
 |
|
|
|
|
Q5SHP7
(RS17_THET8) -
30S ribosomal protein S17
|
|
|
|
Seq: Struc:
|
 |
 |
 |
105 a.a.
104 a.a.*
|
|
|
|
|
|
|
 |
 |
|
|
|
|
Q5SLQ0
(RS18_THET8) -
30S ribosomal protein S18
|
|
|
|
Seq: Struc:
|
 |
 |
 |
88 a.a.
73 a.a.*
|
|
|
|
|
|
|
 |
 |
|
|
|
|
Q5SHP2
(RS19_THET8) -
30S ribosomal protein S19
|
|
|
|
Seq: Struc:
|
 |
 |
 |
93 a.a.
84 a.a.
|
|
|
|
|
|
|
 |
 |
|
 |
|
 |
|
 |
|
|
Gene Ontology (GO) functional annotation
|
|
|
|
 |
 |
 |
|
 |
 |
 |
 |
|
 |
|
Cellular component
|
intracellular
|
4 terms
|
 |
|
Biological process
|
translation
|
1 term
|
 |
|
Biochemical function
|
structural constituent of ribosome
|
6 terms
|
 |
|
|
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
|
|
|
| |
|
DOI no:
|
Nature
407:340-348
(2000)
|
|
PubMed id:
|
|
|
|
|
| |
|
Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics.
|
|
A.P.Carter,
W.M.Clemons,
D.E.Brodersen,
R.J.Morgan-Warren,
B.T.Wimberly,
V.Ramakrishnan.
|
|
|
|
| |
ABSTRACT
|
|
|
| |
|
The 30S ribosomal subunit has two primary functions in protein synthesis. It
discriminates against aminoacyl transfer RNAs that do not match the codon of
messenger RNA, thereby ensuring accuracy in translation of the genetic message
in a process called decoding. Also, it works with the 50S subunit to move the
tRNAs and associated mRNA by precisely one codon, in a process called
translocation. Here we describe the functional implications of the
high-resolution 30S crystal structure presented in the accompanying paper, and
infer details of the interactions between the 30S subunit and its tRNA and mRNA
ligands. We also describe the crystal structure of the 30S subunit complexed
with the antibiotics paromomycin, streptomycin and spectinomycin, which
interfere with decoding and translocation. This work reveals the structural
basis for the action of these antibiotics, and leads to a model for the role of
the universally conserved 16S RNA residues A1492 and A1493 in the decoding
process.
|
|
|
|
|
| |
Selected figure(s)
|
|
|
| |
 |
 |
|
 |
|
 |
Figure 4.
Figure 4: Interaction of spectinomycin with the 30S ribosomal
subunit. a, Difference Fourier maps showing the binding site
of spectinomycin in helix 34. b, Chemical structure of
spectinomycin, showing interactions of the various groups with
specific residues of 30S. c, The spectinomycin-binding site,
showing its location at a pivotal point in the head of the 30S
subunit. d, Inset showing spectinomycin in a space-filling
model, and the location of its binding site on the 30S.
|
 |
Figure 5.
Figure 5: Interaction of streptomycin with the 30S ribosomal
subunit. a, Difference Fourier maps showing the binding site
of streptomycin. Mutations in ribosomal protein S12 that confer
resistance are shown in red. b, Chemical structure of
streptomycin, showing interactions of the various groups with
specific residues of the ribosome. c, The streptomycin-binding
site, showing its interaction with H27, the 530 loop (H18), H44
and ribosomal protein S12. d, A view of the 30S showing
streptomycin in a space-filling model, and the surrounding RNA
and protein elements.
|
 |
|
|
|
| |
The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2000,
407,
340-348)
copyright 2000.
|
|
| |
Figures were
selected
by the author.
|
|
|
|
|
 |
 |
|
 |
 |
 |
 |
 |
 |
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
 |
| |
PubMed id
|
 |
Reference
|
 |
|
|
|
 |
C.W.Lee,
L.Li,
and
D.P.Giedroc
(2011).
The solution structure of coronaviral stem-loop 2 (SL2) reveals a canonical CUYG tetraloop fold.
|
| |
FEBS Lett, 585,
1049-1053.
|
 |
|
PDB code:
|
 |
|
|
|
|
|
 |
J.Liang,
F.Zeng,
A.Guo,
L.Liu,
N.Guo,
L.Li,
J.Jin,
X.Wu,
M.Liu,
D.Zhao,
Y.Li,
Q.Jin,
and
L.Yu
(2011).
Microarray analysis of the chelerythrine-induced transcriptome of Mycobacterium tuberculosis.
|
| |
Curr Microbiol, 62,
1200-1208.
|
 |
|
|
|
|
 |
N.Husain,
S.Obranic,
L.Koscinski,
J.Seetharaman,
F.Babic,
J.M.Bujnicki,
G.Maravic-Vlahovicek,
and
J.Sivaraman
(2011).
Structural basis for the methylation of A1408 in 16S rRNA by a panaminoglycoside resistance methyltransferase NpmA from a clinical isolate and analysis of the NpmA interactions with the 30S ribosomal subunit.
|
| |
Nucleic Acids Res, 39,
1903-1918.
|
 |
|
PDB codes:
|
 |
|
|
|
|
|
 |
P.B.Klimov,
and
L.L.Knowles
(2011).
Repeated Parallel Evolution of Minimal rRNAs Revealed from Detailed Comparative Analysis.
|
| |
J Hered, 102,
283-293.
|
 |
|
|
|
|
 |
T.Cottin,
C.Pyrkotis,
C.I.Stathakis,
I.Mavridis,
I.A.Katsoulis,
P.Anastasopoulou,
G.Kythreoti,
A.L.Zografos,
V.R.Nahmias,
A.Papakyriakou,
and
D.Vourloumis
(2011).
Designed spiro-bicyclic analogues targeting the ribosomal decoding center.
|
| |
Chembiochem, 12,
71-87.
|
 |
|
|
|
|
 |
V.N.Uversky
(2011).
Multitude of binding modes attainable by intrinsically disordered proteins: a portrait gallery of disorder-based complexes.
|
| |
Chem Soc Rev, 40,
1623-1634.
|
 |
|
|
|
|
 |
Y.Zhang,
and
M.Inouye
(2011).
RatA (YfjG), an Escherichia coli toxin, inhibits 70S ribosome association to block translation initiation.
|
| |
Mol Microbiol, 79,
1418-1429.
|
 |
|
|
|
|
 |
A.E.Scheunemann,
W.D.Graham,
F.A.Vendeix,
and
P.F.Agris
(2010).
Binding of aminoglycoside antibiotics to helix 69 of 23S rRNA.
|
| |
Nucleic Acids Res, 38,
3094-3105.
|
 |
|
|
|
|
 |
A.M.Barnard,
N.J.Simpson,
K.S.Lilley,
and
G.P.Salmond
(2010).
Mutations in rpsL that confer streptomycin resistance show pleiotropic effects on virulence and the production of a carbapenem antibiotic in Erwinia carotovora.
|
| |
Microbiology, 156,
1030-1039.
|
 |
|
|
|
|
 |
A.M.Lopes,
R.N.Miguel,
C.A.Sargent,
P.J.Ellis,
A.Amorim,
and
N.A.Affara
(2010).
The human RPS4 paralogue on Yq11.223 encodes a structurally conserved ribosomal protein and is preferentially expressed during spermatogenesis.
|
| |
BMC Mol Biol, 11,
33.
|
 |
|
|
|
|
 |
A.Tripathi,
and
G.E.Kellogg
(2010).
A novel and efficient tool for locating and characterizing protein cavities and binding sites.
|
| |
Proteins, 78,
825-842.
|
 |
|
|
|
|
 |
B.Sander,
M.M.Golas,
R.Lührmann,
and
H.Stark
(2010).
An approach for de novo structure determination of dynamic molecular assemblies by electron cryomicroscopy.
|
| |
Structure, 18,
667-676.
|
 |
|
|
|
|
 |
C.L.Ng,
K.Lang,
N.A.Meenan,
A.Sharma,
A.C.Kelley,
C.Kleanthous,
and
V.Ramakrishnan
(2010).
Structural basis for 16S ribosomal RNA cleavage by the cytotoxic domain of colicin E3.
|
| |
Nat Struct Mol Biol, 17,
1241-1246.
|
 |
|
|
|
|
 |
D.B.Craig,
A.M.Haslam,
H.J.Silverstein,
M.Chikamatsu,
E.Shadabi,
and
E.R.Nichols
(2010).
Effect of size, quaternary structure and translational error on the static and dynamic heterogeneity of beta-galactosidase and measurement of electrophoretic dynamic heterogeneity.
|
| |
Protein J, 29,
398-406.
|
 |
|
|
|
|
 |
D.Balenci,
N.D'Amelio,
E.Gaggelli,
N.Gaggelli,
L.Cellai,
E.Molteni,
and
G.Valensin
(2010).
Structural features of apramycin bound at the bacterial ribosome a site as detected by NMR and CD spectroscopy.
|
| |
Chembiochem, 11,
166-169.
|
 |
|
|
|
|
 |
E.B.Kramer,
H.Vallabhaneni,
L.M.Mayer,
and
P.J.Farabaugh
(2010).
A comprehensive analysis of translational missense errors in the yeast Saccharomyces cerevisiae.
|
| |
RNA, 16,
1797-1808.
|
 |
|
|
|
|
 |
E.C.Böttger
(2010).
Mutant A1555G mitochondrial 12S rRNA and aminoglycoside susceptibility.
|
| |
Antimicrob Agents Chemother, 54,
3073.
|
 |
|
|
|
|
 |
E.Ennifar,
P.Walter,
and
P.Dumas
(2010).
Cation-dependent cleavage of the duplex form of the subtype-B HIV-1 RNA dimerization initiation site.
|
| |
Nucleic Acids Res, 38,
5807-5816.
|
 |
|
|
|
|
 |
G.De Pascale,
and
G.D.Wright
(2010).
Antibiotic resistance by enzyme inactivation: from mechanisms to solutions.
|
| |
Chembiochem, 11,
1325-1334.
|
 |
|
|
|
|
 |
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.
|
 |
|
|
|
|
 |
J.Frank,
and
R.L.Gonzalez
(2010).
Structure and dynamics of a processive Brownian motor: the translating ribosome.
|
| |
Annu Rev Biochem, 79,
381-412.
|
 |
|
|
|
|
 |
J.L.Houghton,
K.D.Green,
W.Chen,
and
S.Garneau-Tsodikova
(2010).
The future of aminoglycosides: the end or renaissance?
|
| |
Chembiochem, 11,
880-902.
|
 |
|
|
|
|
 |
L.Bidou,
J.P.Rousset,
and
O.Namy
(2010).
Translational errors: from yeast to new therapeutic targets.
|
| |
FEMS Yeast Res, 10,
1070-1082.
|
 |
|
|
|
|
 |
L.E.Via,
S.N.Cho,
S.Hwang,
H.Bang,
S.K.Park,
H.S.Kang,
D.Jeon,
S.Y.Min,
T.Oh,
Y.Kim,
Y.M.Kim,
V.Rajan,
S.Y.Wong,
I.C.Shamputa,
M.Carroll,
L.Goldfeder,
S.A.Lee,
S.M.Holland,
S.Eum,
H.Lee,
and
C.E.Barry
(2010).
Polymorphisms Associated with Resistance and Cross-Resistance to Aminoglycosides and Capreomycin in Mycobacterium tuberculosis Isolates from South Korean Patients with Drug-Resistant Tuberculosis.
|
| |
J Clin Microbiol, 48,
402-411.
|
 |
|
|
|
|
 |
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.
|
 |
|
|
|
|
 |
M.Morar,
and
G.D.Wright
(2010).
The genomic enzymology of antibiotic resistance.
|
| |
Annu Rev Genet, 44,
25-51.
|
 |
|
|
|
|
 |
M.Toth,
S.Vakulenko,
and
C.A.Smith
(2010).
Purification, crystallization and preliminary X-ray analysis of Enterococcus casseliflavus aminoglycoside-2''-phosphotransferase-IVa.
|
| |
Acta Crystallogr Sect F Struct Biol Cryst Commun, 66,
81-84.
|
 |
|
|
|
|
 |
M.V.Rodnina,
and
W.Wintermeyer
(2010).
The ribosome goes Nobel.
|
| |
Trends Biochem Sci, 35,
1-5.
|
 |
|
|
|
|
 |
N.B.Hammond,
B.S.Tolbert,
R.Kierzek,
D.H.Turner,
and
S.D.Kennedy
(2010).
RNA internal loops with tandem AG pairs: the structure of the 5'GAGU/3'UGAG loop can be dramatically different from others, including 5'AAGU/3'UGAA.
|
| |
Biochemistry, 49,
5817-5827.
|
 |
|
PDB codes:
|
 |
|
|
|
|
|
 |
Q.Yang,
G.M.Gilmartin,
and
S.Doublié
(2010).
Structural basis of UGUA recognition by the Nudix protein CFI(m)25 and implications for a regulatory role in mRNA 3' processing.
|
| |
Proc Natl Acad Sci U S A, 107,
10062-10067.
|
 |
|
PDB codes:
|
 |
|
|
|
|
|
 |
R.E.Stanley,
G.Blaha,
R.L.Grodzicki,
M.D.Strickler,
and
T.A.Steitz
(2010).
The structures of the anti-tuberculosis antibiotics viomycin and capreomycin bound to the 70S ribosome.
|
| |
Nat Struct Mol Biol, 17,
289-293.
|
 |
|
PDB codes:
|
 |
|
|
|
|
|
 |
R.P.Rambo,
and
J.A.Tainer
(2010).
Improving small-angle X-ray scattering data for structural analyses of the RNA world.
|
| |
RNA, 16,
638-646.
|
 |
|
|
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