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PDBsum entry 1nqx
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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A structure-Based model of the reaction catalyzed by lumazine synthase from aquifex aeolicus.
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Authors
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X.Zhang,
W.Meining,
M.Cushman,
I.Haase,
M.Fischer,
A.Bacher,
R.Ladenstein.
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Ref.
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J Mol Biol, 2003,
328,
167-182.
[DOI no: ]
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PubMed id
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Abstract
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6,7-Dimethyl-8-ribityllumazine is the biosynthetic precursor of riboflavin,
which, as a coenzyme, plays a vital role in the electron transfer process for
energy production in all cellular organisms. The enzymes involved in lumazine
biosynthesis have been studied in considerable detail. However, the conclusive
mechanism of the reaction catalyzed by lumazine synthase has remained unclear.
Here, we report four crystal structures of the enzyme from the hyperthermophilic
bacterium Aquifex aeolicus in complex with different inhibitor compounds. The
structures were refined at resolutions of 1.72 A, 1.85 A, 2.05 A and 2.2 A,
respectively. The inhibitors have been designed in order to mimic the substrate,
the putative reaction intermediates and the final product. Structural
comparisons of the native enzyme and the inhibitor complexes as well as the
kinetic data of single-site mutants of lumazine synthase from Bacillus subtilis
showed that several highly conserved residues at the active site, namely Phe22,
His88, Arg127, Lys135 and Glu138 are most likely involved in catalysis. A
structural model of the catalytic process, which illustrates binding of
substrates, enantiomer specificity, proton abstraction/donation, inorganic
phosphate elimination, formation of the Schiff base and cyclization is proposed.
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Figure 3.
Figure 3. The 2F[o] -F[c] electron densitiy (s=1.5) around
the active site of A. aeolicus lumazine synthase in complex with
the product analogue 6,7-dioxo-5H-8-ribitylaminolumazine (RDL).
The average B-factor of water molecules, indicated by red
spheres, is below 21 Å2.
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Figure 8.
Figure 8. Hypothetical mechanism for the biosynthesis of
lumazine suggested by Kis et al.[12.]
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2003,
328,
167-182)
copyright 2003.
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