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PDBsum entry 3c3e
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References listed in PDB file
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Key reference
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Title
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Molecular insights into the biosynthesis of the f420 coenzyme.
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Authors
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F.Forouhar,
M.Abashidze,
H.Xu,
L.L.Grochowski,
J.Seetharaman,
M.Hussain,
A.Kuzin,
Y.Chen,
W.Zhou,
R.Xiao,
T.B.Acton,
G.T.Montelione,
A.Galinier,
R.H.White,
L.Tong.
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Ref.
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J Biol Chem, 2008,
283,
11832-11840.
[DOI no: ]
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PubMed id
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Abstract
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Coenzyme F(420), a hydride carrier, is found in Archaea and some bacteria and
has crucial roles in methanogenesis, antibiotic biosynthesis, DNA repair, and
activation of antitubercular compounds. CofD, 2-phospho-l-lactate transferase,
catalyzes the last step in the biosynthesis of F(420)-0 (F(420) without
polyglutamate), by transferring the lactyl phosphate moiety of
lactyl(2)diphospho-(5')guanosine to 7,8-didemethyl-8-hydroxy-5-deazariboflavin
ribitol (Fo). CofD is highly conserved among F(420)-producing organisms, and
weak sequence homologs are also found in non-F(420)-producing organisms. This
superfamily does not share any recognizable sequence conservation with other
proteins. Here we report the first crystal structures of CofD, the free enzyme
and two ternary complexes, with Fo and P(i) or with Fo and GDP, from
Methanosarcina mazei. The active site is located at the C-terminal end of a
Rossmann fold core, and three large insertions make significant contributions to
the active site and dimer formation. The observed binding modes of Fo and GDP
can explain known biochemical properties of CofD and are also supported by our
binding assays. The structures provide significant molecular insights into the
biosynthesis of the F(420) coenzyme. Large structural differences in the active
site region of the non-F(420)-producing CofD homologs suggest that they catalyze
a different biochemical reaction.
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Figure 3.
FIGURE 3. Binding mode of GDP. A, final 2F[o] - F[c]
electron density for GDP molecule, contoured at 1  .
Produced with PyMol (41). B, schematic drawing of the
interactions between GDP and CofD. C, overlay of the structure
of the ternary complex with Fo and GDP (in purple) and that with
Fo and P[i] (in yellow). The P[i] is located about 1 Å
from the  -phosphate of GDP, but
there is a large difference in the conformation of the
glycine-rich loop, indicated with the red star.
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Figure 4.
FIGURE 4. Binding mode of Fo. A, final 2F[o] - F[c]
electron density for Fo, contoured at 1 . Produced with PyMol
(41). B, schematic drawing of the interactions between Fo and
CofD.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2008,
283,
11832-11840)
copyright 2008.
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