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PDBsum entry 1qhs
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* Residue conservation analysis
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Embo J
19:2690-2700
(2000)
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PubMed id:
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The crystal structures of chloramphenicol phosphotransferase reveal a novel inactivation mechanism.
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T.Izard,
J.Ellis.
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ABSTRACT
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Chloramphenicol (Cm), produced by the soil bacterium Streptomyces venezuelae, is
an inhibitor of bacterial ribosomal peptidyltransferase activity. The
Cm-producing streptomycete modifies the primary (C-3) hydroxyl of the antibiotic
by a novel Cm-inactivating enzyme, chloramphenicol 3-O-phosphotransferase (CPT).
Here we describe the crystal structures of CPT in the absence and presence of
bound substrates. The enzyme is dimeric in a sulfate-free solution and
tetramerization is induced by ammonium sulfate, the crystallization precipitant.
The tetrameric quaternary structure exhibits crystallographic 222 symmetry and
has ATP binding pockets located at a crystallographic 2-fold axis. Steric
hindrance allows only one ATP to bind per dimer within the tetramer. In addition
to active site binding by Cm, an electron-dense feature resembling the enzyme's
product is found at the other subunit interface. The structures of CPT suggest
that an aspartate acts as a general base to accept a proton from the 3-hydroxyl
of Cm, concurrent with nucleophilic attack of the resulting oxyanion on the
gamma-phosphate of ATP. Comparison between liganded and substrate-free CPT
structures highlights side chain movements of the active site's Arg136
guanidinium group of >9 A upon substrate binding.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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M.Morar,
and
G.D.Wright
(2010).
The genomic enzymology of antibiotic resistance.
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Annu Rev Genet,
44,
25-51.
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T.Shakya,
and
G.D.Wright
(2010).
Nucleotide selectivity of antibiotic kinases.
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Antimicrob Agents Chemother,
54,
1909-1913.
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Y.Araiso,
R.L.Sherrer,
R.Ishitani,
J.M.Ho,
D.Söll,
and
O.Nureki
(2009).
Structure of a tRNA-dependent kinase essential for selenocysteine decoding.
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Proc Natl Acad Sci U S A,
106,
16215-16220.
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PDB codes:
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H.Sugawara,
N.Ueda,
M.Kojima,
N.Makita,
T.Yamaya,
and
H.Sakakibara
(2008).
Structural insight into the reaction mechanism and evolution of cytokinin biosynthesis.
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Proc Natl Acad Sci U S A,
105,
2734-2739.
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PDB codes:
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R.L.Sherrer,
P.O'Donoghue,
and
D.Söll
(2008).
Characterization and evolutionary history of an archaeal kinase involved in selenocysteinyl-tRNA formation.
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Nucleic Acids Res,
36,
1247-1259.
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U.Kapp,
S.Macedo,
D.R.Hall,
I.Leiros,
S.M.McSweeney,
and
E.Mitchell
(2008).
Structure of Deinococcus radiodurans tunicamycin-resistance protein (TmrD), a phosphotransferase.
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
64,
479-486.
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PDB code:
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J.A.Khan,
S.Xiang,
and
L.Tong
(2007).
Crystal structure of human nicotinamide riboside kinase.
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Structure,
15,
1005-1013.
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PDB codes:
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M.Hashimoto,
T.Taguchi,
S.Nishida,
K.Ueno,
K.Koizumi,
M.Aburada,
and
K.Ichinose
(2007).
Isolation of 8'-phosphate ester derivatives of amicoumacins: structure-activity relationship of hydroxy amino acid moiety.
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J Antibiot (Tokyo),
60,
752-756.
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S.K.Khoo,
B.Loll,
W.T.Chan,
R.L.Shoeman,
L.Ngoo,
C.C.Yeo,
and
A.Meinhart
(2007).
Molecular and structural characterization of the PezAT chromosomal toxin-antitoxin system of the human pathogen Streptococcus pneumoniae.
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J Biol Chem,
282,
19606-19618.
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PDB code:
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A.Yonath
(2005).
Antibiotics targeting ribosomes: resistance, selectivity, synergism and cellular regulation.
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Annu Rev Biochem,
74,
649-679.
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V.S.Hung,
Y.Hatada,
S.Goda,
J.Lu,
Y.Hidaka,
Z.Li,
M.Akita,
Y.Ohta,
K.Watanabe,
H.Matsui,
S.Ito,
and
K.Horikoshi
(2005).
alpha-Glucosidase from a strain of deep-sea Geobacillus: a potential enzyme for the biosynthesis of complex carbohydrates.
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Appl Microbiol Biotechnol,
68,
757-765.
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A.Yonath,
and
A.Bashan
(2004).
Ribosomal crystallography: initiation, peptide bond formation, and amino acid polymerization are hampered by antibiotics.
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Annu Rev Microbiol,
58,
233-251.
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D.Pettigrew,
K.L.Anderson,
J.Billington,
E.Cota,
P.Simpson,
P.Urvil,
F.Rabuzin,
P.Roversi,
B.Nowicki,
L.du Merle,
C.Le Bouguénec,
S.Matthews,
and
S.M.Lea
(2004).
High resolution studies of the Afa/Dr adhesin DraE and its interaction with chloramphenicol.
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J Biol Chem,
279,
46851-46857.
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PDB codes:
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K.N.Rao,
C.G.Suresh,
U.V.Katre,
S.M.Gaikwad,
and
M.I.Khan
(2004).
Two orthorhombic crystal structures of a galactose-specific lectin from Artocarpus hirsuta in complex with methyl-alpha-D-galactose.
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Acta Crystallogr D Biol Crystallogr,
60,
1404-1412.
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PDB codes:
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N.Fernandez-Fuentes,
A.Hermoso,
J.Espadaler,
E.Querol,
F.X.Aviles,
and
B.Oliva
(2004).
Classification of common functional loops of kinase super-families.
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Proteins,
56,
539-555.
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N.N.Suzuki,
K.Koizumi,
M.Fukushima,
A.Matsuda,
and
F.Inagaki
(2004).
Structural basis for the specificity, catalysis, and regulation of human uridine-cytidine kinase.
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Structure,
12,
751-764.
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PDB codes:
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S.Schwarz,
C.Kehrenberg,
B.Doublet,
and
A.Cloeckaert
(2004).
Molecular basis of bacterial resistance to chloramphenicol and florfenicol.
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FEMS Microbiol Rev,
28,
519-542.
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T.Auerbach,
A.Bashan,
and
A.Yonath
(2004).
Ribosomal antibiotics: structural basis for resistance, synergism and selectivity.
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Trends Biotechnol,
22,
570-576.
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N.O'Toole,
J.A.Barbosa,
Y.Li,
L.W.Hung,
A.Matte,
and
M.Cygler
(2003).
Crystal structure of a trimeric form of dephosphocoenzyme A kinase from Escherichia coli.
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Protein Sci,
12,
327-336.
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PDB code:
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T.Izard
(2003).
A novel adenylate binding site confers phosphopantetheine adenylyltransferase interactions with coenzyme A.
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J Bacteriol,
185,
4074-4080.
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PDB code:
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A.Galinier,
J.P.Lavergne,
C.Geourjon,
S.Fieulaine,
S.Nessler,
and
J.M.Jault
(2002).
A new family of phosphotransferases with a P-loop motif.
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J Biol Chem,
277,
11362-11367.
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R.A.Maxwell,
W.H.Welch,
F.M.Horodyski,
K.M.Schegg,
and
D.A.Schooley
(2002).
Juvenile hormone diol kinase. II. Sequencing, cloning, and molecular modeling of juvenile hormone-selective diol kinase from Manduca sexta.
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J Biol Chem,
277,
21882-21890.
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T.Izard
(2001).
Structural basis for chloramphenicol tolerance in Streptomyces venezuelae by chloramphenicol phosphotransferase activity.
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Protein Sci,
10,
1508-1513.
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PDB codes:
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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.
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