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PDBsum entry 1ep2
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Oxidoreductase
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PDB id
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1ep2
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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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Structure of dihydroorotate dehydrogenase b: electron transfer between two flavin groups bridged by an iron-Sulphur cluster.
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Authors
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P.Rowland,
S.Nørager,
K.F.Jensen,
S.Larsen.
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Ref.
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Structure, 2000,
8,
1227-1238.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: The fourth step and only redox reaction in pyrimidine de novo
biosynthesis is catalyzed by the flavoprotein dihydroorotate dehydrogenase
(DHOD). Based on their sequences, DHODs are grouped into two major families.
Lactococcus lactis is one of the few organisms with two DHODs, A and B,
belonging to each of the two subgroups of family 1. The B enzyme (DHODB) is a
prototype for DHODs in Gram-positive bacteria that use NAD+ as the second
substrate. DHODB is a heterotetramer composed of two different proteins (PyrDB
and PyrK) and three different cofactors: FMN, FAD, and a [2Fe-2S] cluster.
RESULTS: Crystal structures have been determined for DHODB and its product
complex. The DHODB heterotetramer is composed of two closely interacting
PyrDB-PyrK dimers with the [2Fe-2S] cluster in their interface centered between
the FMN and FAD groups. Conformational changes are observed between the
complexed and uncomplexed state of the enzyme for the loop carrying the
catalytic cysteine residue and one of the lysines interacting with FMN, which is
important for substrate binding. CONCLUSIONS: A dimer of two PyrDB subunits
resembling the family 1A enzymes forms the central core of DHODB. PyrK belongs
to the NADPH ferredoxin reductase superfamily. The binding site for NAD+ has
been deduced from the similarity to these proteins. The orotate binding in DHODB
is similar to that in the family 1A enzymes. The close proximity of the three
redox centers makes it possible to propose a possible electron transfer pathway
involving residues conserved among the family 1B DHODs.
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Figure 6.
Figure 6. The Environment of the Two Flavin Groups and the
Orotate Binding Site in DHODB(a) The environment of the FMN
group in the uncomplexed PyrDB subunit with an open catalytic
loop. Water molecules are shown as cyan spheres.(b) The
DHODB-orotate complex structure showing the same view of the FMN
group as in Figure 6a and containing a closed but slightly
disordered catalytic loop.(c) A closeup view of the environment
of the bound orotate in the complexed structure.(d) The
environment of the FAD group in PyrK subunit in the uncomplexed
structure. No significant changes were observed in the structure
of the orotate complex
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2000,
8,
1227-1238)
copyright 2000.
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