1ep3
CRYSTAL STRUCTURE OF LACTOCOCCUS LACTIS DIHYDROOROTATE DEHYDROGENASE B. DATA COLLECTED UNDER CRYOGENIC CONDITIONS.
OverviewOverview
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.
About this StructureAbout this Structure
1EP3 is a Protein complex structure of sequences from Lactococcus lactis. Full crystallographic information is available from OCA.
ReferenceReference
Structure of dihydroorotate dehydrogenase B: electron transfer between two flavin groups bridged by an iron-sulphur cluster., Rowland P, Norager S, Jensen KF, Larsen S, Structure. 2000 Dec 15;8(12):1227-38. PMID:11188687 Page seeded by OCA on Fri May 2 15:21:58 2008