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PDBsum entry 4ccn
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Oxidoreductase
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PDB id
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4ccn
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References listed in PDB file
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Key reference
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Title
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Ribosomal oxygenases are structurally conserved from prokaryotes to humans.
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Authors
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R.Chowdhury,
R.Sekirnik,
N.C.Brissett,
T.Krojer,
C.H.Ho,
S.S.Ng,
I.J.Clifton,
W.Ge,
N.J.Kershaw,
G.C.Fox,
J.R.Muniz,
M.Vollmar,
C.Phillips,
E.S.Pilka,
K.L.Kavanagh,
F.Von delft,
U.Oppermann,
M.A.Mcdonough,
A.J.Doherty,
C.J.Schofield.
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Ref.
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Nature, 2014,
510,
422-426.
[DOI no: ]
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PubMed id
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Abstract
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2-Oxoglutarate (2OG)-dependent oxygenases have important roles in the regulation
of gene expression via demethylation of N-methylated chromatin components and in
the hydroxylation of transcription factors and splicing factor proteins.
Recently, 2OG-dependent oxygenases that catalyse hydroxylation of transfer RNA
and ribosomal proteins have been shown to be important in translation relating
to cellular growth, TH17-cell differentiation and translational accuracy. The
finding that ribosomal oxygenases (ROXs) occur in organisms ranging from
prokaryotes to humans raises questions as to their structural and evolutionary
relationships. In Escherichia coli, YcfD catalyses arginine hydroxylation in the
ribosomal protein L16; in humans, MYC-induced nuclear antigen (MINA53; also
known as MINA) and nucleolar protein 66 (NO66) catalyse histidine hydroxylation
in the ribosomal proteins RPL27A and RPL8, respectively. The functional
assignments of ROXs open therapeutic possibilities via either ROX inhibition or
targeting of differentially modified ribosomes. Despite differences in the
residue and protein selectivities of prokaryotic and eukaryotic ROXs, comparison
of the crystal structures of E. coli YcfD and Rhodothermus marinus YcfD with
those of human MINA53 and NO66 reveals highly conserved folds and novel
dimerization modes defining a new structural subfamily of 2OG-dependent
oxygenases. ROX structures with and without their substrates support their
functional assignments as hydroxylases but not demethylases, and reveal how the
subfamily has evolved to catalyse the hydroxylation of different residue side
chains of ribosomal proteins. Comparison of ROX crystal structures with those of
other JmjC-domain-containing hydroxylases, including the hypoxia-inducible
factor asparaginyl hydroxylase FIH and histone N(ε)-methyl lysine demethylases,
identifies branch points in 2OG-dependent oxygenase evolution and distinguishes
between JmjC-containing hydroxylases and demethylases catalysing modifications
of translational and transcriptional machinery. The structures reveal that new
protein hydroxylation activities can evolve by changing the coordination
position from which the iron-bound substrate-oxidizing species reacts. This
coordination flexibility has probably contributed to the evolution of the wide
range of reactions catalysed by oxygenases.
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Secondary reference #1
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Title
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Oxygenase-Catalyzed ribosome hydroxylation occurs in prokaryotes and humans.
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Authors
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W.Ge,
A.Wolf,
T.Feng,
C.H.Ho,
R.Sekirnik,
A.Zayer,
N.Granatino,
M.E.Cockman,
C.Loenarz,
N.D.Loik,
A.P.Hardy,
T.D.Claridge,
R.B.Hamed,
R.Chowdhury,
L.Gong,
C.V.Robinson,
D.C.Trudgian,
M.Jiang,
M.M.Mackeen,
J.S.Mccullagh,
Y.Gordiyenko,
A.Thalhammer,
A.Yamamoto,
M.Yang,
P.Liu-Yi,
Z.Zhang,
M.Schmidt-Zachmann,
B.M.Kessler,
P.J.Ratcliffe,
G.M.Preston,
M.L.Coleman,
C.J.Schofield.
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Ref.
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Nat Chem Biol, 2012,
8,
960-962.
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PubMed id
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