|
|
|
|
 |
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.
|
 |
|
|
|
|
|
|
|
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.
|
 |
|
|
|
|
|
|
|
72 a.a.
|
 |
|
|
|
|
|
|
|
56 a.a.
|
 |
|
|
|
|
|
|
|
46 a.a.
|
 |
|
|
|
|
|
|
|
92 a.a.
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
_SR
×108
|
 |
|
|
|
|
|
|
|
_NA
×75
|
 |
|
|
|
|
|
|
|
_CL
×22
|
 |
|
|
|
|
|
|
|
_CD
×5
|
 |
|
|
|
|
|
|
|
_MG
×92
|
 |
|
|
|
|
|
|
|
__K
×2
|
 |
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
PDB id:
|
 |
|
 |
| Name: |
 |
Ribosome
|
 |
|
Title:
|
 |
The structure of the antibiotic linezolid bound to the large ribosomal subunit of haloarcula marismortui
|
|
Structure:
|
 |
23s ribosomal RNA. Chain: 0. Mutation: yes. 5s ribosomal RNA. Chain: 9. 50s ribosomal protein l2p. Chain: a. 50s ribosomal protein l3p. Chain: b.
|
|
Source:
|
 |
Haloarcula marismortui. Organism_taxid: 2238. Strain: dt41. Halobacterium marismortui. Synthetic: yes
|
|
Resolution:
|
 |
|
2.70Å
|
R-factor:
|
0.191
|
R-free:
|
0.230
|
|
|
Authors:
|
 |
J.A.Ippolito,Z.K.Kanyo,D.Wang,F.J.Franceschi,P.B.Moore,T.A.Steitz, E.M.Duffy
|
|
Key ref:
|
 |
J.A.Ippolito
et al.
(2008).
Crystal structure of the oxazolidinone antibiotic linezolid bound to the 50S ribosomal subunit.
J Med Chem,
51,
3353-3356.
PubMed id:
|
 |
|
Date:
|
 |
|
01-Apr-08
|
Release date:
|
22-Jul-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.
|
|
|
|
|
|
|
|
|
 |
 |
|
|
|
|
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.
72 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:
E.C.?
|
|
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
|
|
|
| |
|
|
J Med Chem
51:3353-3356
(2008)
|
|
PubMed id:
|
|
|
|
|
| |
|
Crystal structure of the oxazolidinone antibiotic linezolid bound to the 50S ribosomal subunit.
|
|
J.A.Ippolito,
Z.F.Kanyo,
D.Wang,
F.J.Franceschi,
P.B.Moore,
T.A.Steitz,
E.M.Duffy.
|
|
|
|
| |
ABSTRACT
|
|
|
| |
|
The oxazolidinone antibacterials target the 50S subunit of prokaryotic
ribosomes. To gain insight into their mechanism of action, the crystal structure
of the canonical oxazolidinone, linezolid, has been determined bound to the
Haloarcula marismortui 50S subunit. Linezolid binds the 50S A-site, near the
catalytic center, which suggests that inhibition involves competition with
incoming A-site substrates. These results provide a structural basis for the
discovery of improved oxazolidinones active against emerging drug-resistant
clinical strains.
|
|
|
|
|
|
|
 |
 |
|
 |
 |
 |
 |
 |
 |
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
 |
| |
PubMed id
|
 |
Reference
|
 |
|
|
|
 |
K.L.Leach,
S.J.Brickner,
M.C.Noe,
and
P.F.Miller
(2011).
Linezolid, the first oxazolidinone antibacterial agent.
|
| |
Ann N Y Acad Sci,
1222,
49-54.
|
 |
|
|
|
|
 |
S.B.Kombian,
and
O.A.Phillips
(2011).
In vitro electrophysiological investigations of the acute effects of linezolid and novel oxazolidinones on central nervous system neurons.
|
| |
Neuroscience,
180,
53-63.
|
 |
|
|
|
|
 |
A.R.Renslo
(2010).
Antibacterial oxazolidinones: emerging structure-toxicity relationships.
|
| |
Expert Rev Anti Infect Ther,
8,
565-574.
|
 |
|
|
|
|
 |
C.H.Ma,
X.F.Li,
Y.An,
and
Y.H.Wen
(2010).
3-[2-(1,3-Benzothia-zol-2-ylsulfan-yl)eth-yl]-1,3-oxazolidin-2-one.
|
| |
Acta Crystallogr Sect E Struct Rep Online,
66,
o2472.
|
 |
|
|
|
|
 |
D.Bongiorno,
F.Campanile,
G.Mongelli,
M.T.Baldi,
R.Provenzani,
S.Reali,
C.Lo Russo,
M.Santagati,
and
S.Stefani
(2010).
DNA methylase modifications and other linezolid resistance mutations in coagulase-negative staphylococci in Italy.
|
| |
J Antimicrob Chemother,
65,
2336-2340.
|
 |
|
|
|
|
 |
F.Fujisaki,
K.Shoji,
M.Shimodouzono,
N.Kashige,
F.Miake,
and
K.Sumoto
(2010).
Antibacterial activity of 5-dialkylaminomethylhydantoins and related compounds.
|
| |
Chem Pharm Bull (Tokyo),
58,
1123-1126.
|
 |
|
|
|
|
 |
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:
|
 |
|
|
|
|
|
 |
A.M.Giessing,
S.S.Jensen,
A.Rasmussen,
L.H.Hansen,
A.Gondela,
K.Long,
B.Vester,
and
F.Kirpekar
(2009).
Identification of 8-methyladenosine as the modification catalyzed by the radical SAM methyltransferase Cfr that confers antibiotic resistance in bacteria.
|
| |
RNA,
15,
327-336.
|
 |
|
|
|
|
 |
D.N.Wilson
(2009).
The A-Z of bacterial translation inhibitors.
|
| |
Crit Rev Biochem Mol Biol,
44,
393-433.
|
 |
|
|
|
|
 |
E.Zimmerman,
and
A.Yonath
(2009).
Biological implications of the ribosome's stunning stereochemistry.
|
| |
Chembiochem,
10,
63-72.
|
 |
|
|
|
|
 |
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.B.Locke,
M.Hilgers,
and
K.J.Shaw
(2009).
Novel ribosomal mutations in Staphylococcus aureus strains identified through selection with the oxazolidinones linezolid and torezolid (TR-700).
|
| |
Antimicrob Agents Chemother,
53,
5265-5274.
|
 |
|
|
|
|
 |
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.
|
| |
Mol Microbiol,
71,
1218-1227.
|
 |
|
|
|
|
 |
L.P.Labuda,
A.Pushechnikov,
and
M.D.Disney
(2009).
Small molecule microarrays of RNA-focused peptoids help identify inhibitors of a pathogenic group I intron.
|
| |
ACS Chem Biol,
4,
299-307.
|
 |
|
|
|
|
 |
V.Kalia,
R.Miglani,
K.P.Purnapatre,
T.Mathur,
S.Singhal,
S.Khan,
S.R.Voleti,
D.J.Upadhyay,
K.S.Saini,
A.Rattan,
and
V.S.Raj
(2009).
Mode of action of Ranbezolid against staphylococci and structural modeling studies of its interaction with ribosomes.
|
| |
Antimicrob Agents Chemother,
53,
1427-1433.
|
 |
|
|
|
|
 |
X.J.Wang,
G.J.Du,
S.Q.Zhao,
M.Yan,
and
L.Q.Gu
(2009).
Synthesis and antibacterial activity of a series of alpha-substituted acetylpiperazinyl oxazolidinones.
|
| |
Chem Biol Drug Des,
74,
276-281.
|
 |
|
|
|
|
 |
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.
|
 |
|
|
|
|
 |
E.Skripkin,
T.S.McConnell,
J.DeVito,
L.Lawrence,
J.A.Ippolito,
E.M.Duffy,
J.Sutcliffe,
and
F.Franceschi
(2008).
R chi-01, a new family of oxazolidinones that overcome ribosome-based linezolid resistance.
|
| |
Antimicrob Agents Chemother,
52,
3550-3557.
|
 |
|
|
|
|
 |
K.J.Shaw,
S.Poppe,
R.Schaadt,
V.Brown-Driver,
J.Finn,
C.M.Pillar,
D.Shinabarger,
and
G.Zurenko
(2008).
In vitro activity of TR-700, the antibacterial moiety of the prodrug TR-701, against linezolid-resistant strains.
|
| |
Antimicrob Agents Chemother,
52,
4442-4447.
|
 |
|
 |
 |
|
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
code is
shown on the right.
|
');
}
}
| |