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DOI no:
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J Biol Chem
275:1814-1822
(2000)
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PubMed id:
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Crystal structure of the gephyrin-related molybdenum cofactor biosynthesis protein MogA from Escherichia coli.
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M.T.Liu,
M.M.Wuebbens,
K.V.Rajagopalan,
H.Schindelin.
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ABSTRACT
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Molybdenum cofactor (Moco) biosynthesis is an evolutionarily conserved pathway
in archaea, eubacteria, and eukaryotes, including humans. Genetic deficiencies
of enzymes involved in this biosynthetic pathway trigger an autosomal recessive
disease with severe neurological symptoms, which usually leads to death in early
childhood. The MogA protein exhibits affinity for molybdopterin, the organic
component of Moco, and has been proposed to act as a molybdochelatase
incorporating molybdenum into Moco. MogA is related to the protein gephyrin,
which, in addition to its role in Moco biosynthesis, is also responsible for
anchoring glycinergic receptors to the cytoskeleton at inhibitory synapses. The
high resolution crystal structure of the Escherichia coli MogA protein has been
determined, and it reveals a trimeric arrangement in which each monomer contains
a central, mostly parallel beta-sheet surrounded by alpha-helices on either
side. Based on structural and biochemical data, a putative active site was
identified, including two residues that are essential for the catalytic
mechanism.
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Selected figure(s)
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Figure 2.
Fig. 2. Ribbon representations of the MogA structure. A,
the MogA monomer viewed perpendicular to the central  -sheet. -Strands are
shown as curved arrows in green, and  -helices
and the 3[10] helix are shown as ribbons in red and blue,
respectively. Secondary structure elements, N and C termini, and
the residues adjacent to the disordered loop are labeled. The
sulfate molecule bound near the TXGGTG motif is indicated. B,
the MogA monomer viewed along the -sheet and
superimposed with a transparent surface representation of the
protein. Note the pocket in the molecular surface located
between 5 and the
3[10] helix. C, structure of the MogA trimer viewed along the
3-fold axis. Each color represents a different monomer. In
addition to the sulfate, the side chains of the strictly
conserved residues Asp-49 and Asp-82 are shown. Figs. 2, 3B, and
5B were produced with Molscript (42) and Raster3D (43).
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Figure 3.
Fig. 3. Structural features of MogA. A, stereo view of
the electron density maps (SIGMAA weighted 2F[o]  F[c] and
F[o] F[c] maps
in blue and red, respectively) near the TXGGTG motif. Note the
density feature extending from one of the sulfate oxygens
(marked by the arrow). An additional unassigned peak is present
at the bottom of the figure. Figs. 3A and 5A were prepared with
SPOCK (44). B, least squares superposition of the NatH1 (dark
gray) and NatH2 (light gray) structures. Residues 107-113 are
shown with their side chains and adjacent regions of the
molecule as C -trace.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2000,
275,
1814-1822)
copyright 2000.
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Figures were
selected
by an automated process.
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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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S.P.Kanaujia,
C.V.Ranjani,
J.Jeyakanthan,
S.Baba,
L.Chen,
Z.J.Liu,
B.C.Wang,
M.Nishida,
A.Ebihara,
A.Shinkai,
S.Kuramitsu,
Y.Shiro,
K.Sekar,
and
S.Yokoyama
(2007).
Crystallization and preliminary crystallographic analysis of molybdenum-cofactor biosynthesis protein C from Thermus thermophilus.
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Acta Crystallogr Sect F Struct Biol Cryst Commun, 63,
27-29.
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E.Y.Kim,
N.Schrader,
B.Smolinsky,
C.Bedet,
C.Vannier,
G.Schwarz,
and
H.Schindelin
(2006).
Deciphering the structural framework of glycine receptor anchoring by gephyrin.
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EMBO J, 25,
1385-1395.
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PDB codes:
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G.Bader,
M.Gomez-Ortiz,
C.Haussmann,
A.Bacher,
R.Huber,
and
M.Fischer
(2004).
Structure of the molybdenum-cofactor biosynthesis protein MoaB of Escherichia coli.
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Acta Crystallogr D Biol Crystallogr, 60,
1068-1075.
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PDB code:
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M.Sola,
V.N.Bavro,
J.Timmins,
T.Franz,
S.Ricard-Blum,
G.Schoehn,
R.W.Ruigrok,
I.Paarmann,
T.Saiyed,
G.A.O'Sullivan,
B.Schmitt,
H.Betz,
and
W.Weissenhorn
(2004).
Structural basis of dynamic glycine receptor clustering by gephyrin.
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EMBO J, 23,
2510-2519.
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PDB code:
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C.Sandu,
and
R.Brandsch
(2002).
Functional analysis of the Escherichia coli molybdopterin cofactor biosynthesis protein MoeA by site-directed mutagenesis.
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Biol Chem, 383,
319-323.
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I.S.Heck,
J.D.Schrag,
J.Sloan,
L.J.Millar,
G.Kanan,
J.R.Kinghorn,
and
S.E.Unkles
(2002).
Mutational analysis of the gephyrin-related molybdenum cofactor biosynthetic gene cnxE from the lower eukaryote Aspergillus nidulans.
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Genetics, 161,
623-632.
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J.Kuper,
T.Palmer,
R.R.Mendel,
and
G.Schwarz
(2000).
Mutations in the molybdenum cofactor biosynthetic protein Cnx1G from Arabidopsis thaliana define functions for molybdopterin binding, molybdenum insertion, and molybdenum cofactor stabilization.
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Proc Natl Acad Sci U S A, 97,
6475-6480.
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M.Ramming,
S.Kins,
N.Werner,
A.Hermann,
H.Betz,
and
J.Kirsch
(2000).
Diversity and phylogeny of gephyrin: tissue-specific splice variants, gene structure, and sequence similarities to molybdenum cofactor-synthesizing and cytoskeleton-associated proteins.
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Proc Natl Acad Sci U S A, 97,
10266-10271.
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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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185 a.a.
