Substrate Binding Induces Domain Movements in Orotidine 5'-Monophosphate Decarboxylase

Research output: Contribution to journalJournal article

Pernille Hanne Harris, Jens-Christian Navarro Poulsen, Kaj Frank Jensen, Sine Larsen

Orotidine 5'-monophosphate decarboxylase (ODCase) catalyses the decarboxylation of orotidine 5'-monophosphate to uridine 5'-monophosphate (UMP). We have earlier determined the structure of ODCase from Escherichia coli complexed with the inhibitor 1-(5'-phospho-ß-Image -ribofuranosyl)barbituric acid (BMP); here we present the 2.5 Å structure of the uncomplexed apo enzyme, determined from twinned crystals. A structural analysis and comparison of the two structures of the E. coli enzyme show that binding of the inhibitor is accompanied by significant domain movements of approximately 12° around a hinge that crosses the active site. Hence, the ODCase dimer, which contains two active sites, may be divided in three domains: a central domain that is fixed, and two lids which independently move 12° upon binding. Corresponding analyses, presented herein, of the two Saccharomyces cerevisiae ODCase structures (with and without BMP) and the Methanobacterium thermoautotrophicum ODCase structures (with and without 6-aza UMP) show very similar, but somewhat smaller domain movements. The domain movements seem to be initiated by the phosphoryl binding to the enzyme and can explain why the binding of the phosphoryl group is essential for the catalytic function.
Original languageEnglish
JournalJournal of Molecular Biology
Issue number4
Pages (from-to)1019-1029
Publication statusPublished - 2002

Bibliographical note

Author Keywords: domain movements; orotidine 5'-monophosphate decarboxylase; substrate binding; twinning; catalysis

ID: 78979