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PDBsum entry 2b98
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References listed in PDB file
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Key reference
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Title
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Crystal structure of an archaeal pentameric riboflavin synthase in complex with a substrate analog inhibitor: stereochemical implications.
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Authors
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A.Ramsperger,
M.Augustin,
A.K.Schott,
S.Gerhardt,
T.Krojer,
W.Eisenreich,
B.Illarionov,
M.Cushman,
A.Bacher,
R.Huber,
M.Fischer.
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Ref.
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J Biol Chem, 2006,
281,
1224-1232.
[DOI no: ]
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PubMed id
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Abstract
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Whereas eubacterial and eukaryotic riboflavin synthases form homotrimers,
archaeal riboflavin synthases from Methanocaldococcus jannaschii and
Methanothermobacter thermoautrophicus are homopentamers with sequence similarity
to the 6,7-dimethyl-8-ribityllumazine synthase catalyzing the penultimate step
in riboflavin biosynthesis. Recently it could be shown that the complex
dismutation reaction catalyzed by the pentameric M. jannaschii riboflavin
synthase generates riboflavin with the same regiochemistry as observed for
trimeric riboflavin synthases. Here we present crystal structures of the
pentameric riboflavin synthase from M. jannaschii and its complex with the
substrate analog inhibitor, 6,7-dioxo-8-ribityllumazine. The complex structure
shows five active sites located between adjacent monomers of the pentamer. Each
active site can accommodate two substrate analog molecules in anti-parallel
orientation. The topology of the two bound ligands at the active site is well in
line with the known stereochemistry of a pentacyclic adduct of
6,7-dimethyl-8-ribityllumazine that has been shown to serve as a kinetically
competent intermediate. The pentacyclic intermediates of trimeric and pentameric
riboflavin synthases are diastereomers.
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Figure 1.
Terminal reactions of the pathway of riboflavin biosynthesis.
1, 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione; 2,
3,4-dihydroxy-2-butanone 4-phosphate; 3,
6,7-dimethyl-8-ribityllumazine; 4, riboflavin.
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Figure 2.
A, ribbon presentation of a M. jannaschii riboflavin synthase
monomer. B, structural alignment of a M. jannaschii riboflavin
synthase monomer (red) with S. pombe lumazine synthase (green;
Protein Data Bank entry code 1KYZ (38)). C, stereo ribbon
presentation of the M. jannaschii riboflavin synthase pentamer
in complex with 6,7-dioxo-8-ribityllumazine (red) viewed along
the 5-fold non-crystallographic symmetry axis. Individual
subunits are shown in different colors.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2006,
281,
1224-1232)
copyright 2006.
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