|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
237 a.a.
|
 |
|
|
|
|
|
|
|
337 a.a.
|
 |
|
|
|
|
|
|
|
246 a.a.
|
 |
|
|
|
|
|
|
|
140 a.a.
|
 |
|
|
|
|
|
|
|
172 a.a.
|
 |
|
|
|
|
|
|
|
119 a.a.
|
 |
|
|
|
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|
|
29 a.a.
|
 |
|
|
|
|
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|
|
160 a.a.
|
 |
|
|
|
|
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|
|
70 a.a.
|
 |
|
|
|
|
|
|
|
142 a.a.
|
 |
|
|
|
|
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|
|
132 a.a.
|
 |
|
|
|
|
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|
|
145 a.a.
|
 |
|
|
|
|
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|
|
194 a.a.
|
 |
|
|
|
|
|
|
|
186 a.a.
|
 |
|
|
|
|
|
|
|
115 a.a.
|
 |
|
|
|
|
|
|
|
143 a.a.
|
 |
|
|
|
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|
|
95 a.a.
|
 |
|
|
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|
|
150 a.a.
|
 |
|
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|
81 a.a.
|
 |
|
|
|
|
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|
|
119 a.a.
|
 |
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|
|
53 a.a.
|
 |
|
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|
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|
|
65 a.a.
|
 |
|
|
|
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|
|
154 a.a.
|
 |
|
|
|
|
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|
|
82 a.a.
|
 |
|
|
|
|
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|
|
142 a.a.
|
 |
|
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|
|
73 a.a.
|
 |
|
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|
56 a.a.
|
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|
46 a.a.
|
 |
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|
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|
|
92 a.a.
|
 |
|
|
|
|
|
|
|
|
|
|
_SR
×108
|
 |
|
|
|
|
|
|
|
_NA
×75
|
 |
|
|
|
|
|
|
|
_CL
×22
|
 |
|
|
|
|
|
|
|
_MG
×93
|
 |
|
|
|
|
|
|
|
_CD
×5
|
 |
|
|
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|
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|
|
__K
×2
|
 |
|
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|
|
* Residue conservation analysis
|
|
|
|
|
PDB id:
|
 |
|
 |
| Name: |
 |
Ribosome
|
 |
|
Title:
|
 |
Structure of anisomycin resistant 50s ribosomal subunit: 23s rrna mutation a2488u
|
|
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. Organism_taxid: 2238. Organism_taxid: 2238
|
|
Resolution:
|
 |
|
2.90Å
|
R-factor:
|
0.186
|
R-free:
|
0.233
|
|
|
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:
DOI:
|
 |
|
Date:
|
 |
|
26-Feb-08
|
Release date:
|
20-May-08
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
Headers
|
 |
|
|
References
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.*
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
|
|
|
|
|
|
|
|
|
 |
 |
|
 |
|
|
 |
 |
 |
 |
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.?
|
|
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
|
|
|
| |
|
DOI no:
|
J Mol Biol
379:505-519
(2008)
|
|
PubMed id:
|
|
|
|
|
| |
|
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
|
 |
|
|
|
 |
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:
|
 |
|
|
|
|
|
 |
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:
|
 |
|
|
|
|
|
 |
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.
|
 |
|
|
|
|
 |
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.
|
 |
|
|
|
|
 |
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.
|
 |
|
|
|
|
 |
D.N.Wilson
(2009).
The A-Z of bacterial translation inhibitors.
|
| |
Crit Rev Biochem Mol Biol,
44,
393-433.
|
 |
|
|
|
|
 |
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:
|
 |
|
|
|
|
|
 |
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:
|
 |
|
|
|
|
|
 |
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.
|
 |
|
|
|
|
 |
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.
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Mol Microbiol,
71,
1218-1227.
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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.
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Nucleic Acids Res,
36,
6187-6198.
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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.
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Proc Natl Acad Sci U S A,
105,
13339-13344.
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PDB code:
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