|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
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.
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
_SR
×108
|
 |
|
|
|
|
|
|
|
_NA
×75
|
 |
|
|
|
|
|
|
|
_MG
×93
|
 |
|
|
|
|
|
|
|
_CL
×22
|
 |
|
|
|
|
|
|
|
_CD
×5
|
 |
|
|
|
|
|
|
|
__K
×2
|
 |
|
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|
|
* Residue conservation analysis
|
|
|
|
|
PDB id:
|
 |
|
 |
| Name: |
 |
Ribosome
|
 |
|
Title:
|
 |
Co-crystal structure of homoharringtonine bound to the large ribosomal subunit
|
|
Structure:
|
 |
23s ribosomal RNA. Chain: 0. Fragment: residues 2634210-2637132. 50s ribosomal protein l2p. Chain: a. Fragment: residues 143-264. Synonym: hmal2, hl4. 50s ribosomal protein l3p. Chain: b.
|
|
Source:
|
 |
Haloarcula marismortui. Organism_taxid: 2238. Organism_taxid: 2238
|
|
Resolution:
|
 |
|
2.70Å
|
R-factor:
|
0.190
|
R-free:
|
0.229
|
|
|
Authors:
|
 |
G.Gurel,G.Blaha,P.B.Moore,T.A.Steitz
|
Key ref:
|
 |
G.Gürel
et al.
(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.
PubMed id:
DOI:
|
 |
|
Date:
|
 |
|
06-Feb-09
|
Release date:
|
28-Apr-09
|
|
|
|
|
|
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
389:146-156
(2009)
|
|
PubMed id:
|
|
|
|
|
| |
|
U2504 determines the species specificity of the A-site cleft antibiotics: the structures of tiamulin, homoharringtonine, and bruceantin bound to the ribosome.
|
|
G.Gürel,
G.Blaha,
P.B.Moore,
T.A.Steitz.
|
|
|
|
| |
ABSTRACT
|
|
|
| |
|
Structures have been obtained for the complexes that tiamulin,
homoharringtonine, and bruceantin form with the large ribosomal subunit of
Haloarcula marismortui at resolutions ranging from 2.65 to 3.2 A. They show that
all these inhibitors block protein synthesis by competing with the amino acid
side chains of incoming aminoacyl-tRNAs for binding in the A-site cleft in the
peptidyl-transferase center, which is universally conserved. In addition, these
structures support the hypothesis that the species specificity exhibited by the
A-site cleft inhibitors is determined by the interactions they make, or fail to
make, with a single nucleotide, U2504 (Escherichia coli). In the ribosome, the
position of U2504 is controlled by its interactions with neighboring
nucleotides, whose identities vary among kingdoms.
|
|
|
|
|
| |
Selected figure(s)
|
|
|
| |
 |
 |
|
 |
|
 |
Figure 2.
Fig. 2. The chemical structures of tiamulin,
homoharringtonine, and bruceantin and the corresponding
difference electron density. Panels (a)–(c) show the chemical
structures of these inhibitors. Panels (d)–(f) show the
feature in the appropriate (F[o] − F[o]) difference electron
density map that was assigned to the three drugs, with the
structures of the drugs superimposed on them. Difference
electron density maps were contoured at 3σ. Residues forming
the A-site cleft are shown in cyan, and 23S rRNA bases are
numbered to correspond with the 23S rRNA of E. coli.
|
 |
Figure 6.
Fig. 6. Choosing the correct homoharringtonine enantiomer. A
stereo pair that compares the fit of the refined
homoharringtonine structure (gold) to the electron density for
that drug with the fit obtained for the homoharringtonine
structure obtained from the CSD (green), which is its
enantiomer, is provided. The electron density shown is F[o] −
F[o] difference electron density contoured at 3σ.
|
 |
|
|
|
| |
The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2009,
389,
146-156)
copyright 2009.
|
|
| |
Figures were
selected
by an automated process.
|
|
|
|
|
 |
 |
|
 |
 |
 |
 |
 |
 |
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
 |
| |
PubMed id
|
 |
Reference
|
 |
|
|
|
 |
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.
|
 |
|
|
|
|
 |
R.Chen,
L.Guo,
Y.Chen,
Y.Jiang,
W.G.Wierda,
and
W.Plunkett
(2011).
Homoharringtonine reduced Mcl-1 expression and induced apoptosis in chronic lymphocytic leukemia.
|
| |
Blood,
117,
156-164.
|
 |
|
|
|
|
 |
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.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:
|
 |
|
|
|
|
|
 |
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.
|
 |
|
|
|
|
 |
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:
|
 |
|
|
|
|
|
 |
T.Schneider-Poetsch,
T.Usui,
D.Kaida,
and
M.Yoshida
(2010).
Garbled messages and corrupted translations.
|
| |
Nat Chem Biol,
6,
189-198.
|
 |
|
|
|
|
 |
D.N.Wilson
(2009).
The A-Z of bacterial translation inhibitors.
|
| |
Crit Rev Biochem Mol Biol,
44,
393-433.
|
 |
|
|
|
|
 |
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:
|
 |
|
|
 |
 |
|
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.
|
');
}
}
| |