+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Substrate binding induces domain movements in orotidine 5'-monophosphate decarboxylase



Substrate binding induces domain movements in orotidine 5'-monophosphate decarboxylase



Journal of Molecular Biology 318(4): 1019-1029



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-beta-d-ribofuranosyl)barbituric acid (BMP); here we present the 2.5 A 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 degrees 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 degrees 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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 009988951

Download citation: RISBibTeXText

PMID: 12054799

DOI: 10.1016/S0022-2836(02)00200-0


Related references

A reexamination of the substrate utilization of 2-thioorotidine-5'-monophosphate by yeast orotidine-5'-monophosphate decarboxylase. Bioorganic Chemistry 29(2): 96-106, 2001

Isolation and characterization of the orotidine 5'-monophosphate decarboxylase domain of the multifunctional protein uridine 5'-monophosphate synthase. Journal of Biological Chemistry 260(16): 9443-9451, 1985

Substrate specificity of orotidine 5 monophosphate decarboxylase. FASEB Journal 4(7): A1835, 1990

The mechanism of orotidine 5'-monophosphate decarboxylase: Catalysis by destabilization of the substrate. Biochemistry 39(7): 1778-1783, Feb 22, 2000

Substrate distortion contributes to the catalysis of orotidine 5'-monophosphate decarboxylase. Journal of the American Chemical Society 135(46): 17432-17443, 2014

Activation of orotidine 5'-monophosphate decarboxylase by phosphite dianion: the whole substrate is the sum of two parts. Journal of the American Chemical Society 127(45): 15708-9, 2005

Isolation and characterization of the orotidine 5' monophosphate decarboxylase ec 4.1.1.23 domain of the multifunctional protein ump. Journal of Biological Chemistry 260(16): 9443-9451, 1985

Mechanism of the orotidine 5'-monophosphate decarboxylase-catalyzed reaction: evidence for substrate destabilization. Biochemistry 48(24): 5518-5531, 2009

Study of a deletion mutant of the orotidine 5 monophosphate decarboxylase odcase domain of mouse ump synthase. FASEB Journal 4(7): A1835, 1990

Structural characterization of the molecular events during a slow substrate-product transition in orotidine 5'-monophosphate decarboxylase. Journal of Molecular Biology 387(5): 1199-1210, 2009

Effects of substance binding determinants in the transition state for orotidine 5'-monophosphate decarboxylase. Bioorganic Chemistry 26(5): 283-288, 1998

Polarization in the structures of uracil and thiouracils: Implication for binding with orotidine 5'-monophosphate decarboxylase. Bioorganic and Medicinal Chemistry Letters 21(21): 6341-6342, 2012

Expression and sequence analysis of a cDNA encoding the orotidine-5'-monophosphate decarboxylase domain from Ehrlich ascites uridylate synthase. Journal of Biological Chemistry 261(9): 4276-4282, 1986