Disease relevance of Orotidine monophosphate

• The crystal structure of Bacillus subtilis orotidine 5'-monophosphate (OMP) decarboxylase with bound uridine 5'-monophosphate has been determined by multiple wavelength anomalous diffraction phasing techniques and refined to an R-factor of 19.3% at 2.4 A resolution [1].
• A cDNA encoding Cryptococcus neoformans orotidine monophosphate pyrophosphorylase (OMPPase) has been isolated by complementation of the cognate Escherichia coli pyrE mutant [2].
• The orotidine-5'-monophosphate decarboxylase gene of Myxococcus xanthus. Comparison to the OMP decarboxylase gene family [3].
• The 2.6-A structure of the Salmonella typhimurium orotate phosphoribosyltransferase (OPRTase) complexed with its product orotidine monophosphate (OMP) provides the first detailed image of a member of this group of enzymes [4].
• Inhibitors of orotidine monophosphate decarboxylase (ODCase) have applications in RNA viral, parasitic, and other infectious diseases [5].

High impact information on Orotidine monophosphate

• The energy released from protein conformation relaxation provides the predominant contribution to the rate enhancement of orotidine 5'-monophosphate decarboxylase [6].
• Molecular dynamics simulations have been used to derive the structures of ground (orotidine-5'-monophosphate decarboxylase x orotidine 5'-monophosphate; ODC x OMP) and intermediate (ODC x intermediate; ODC x I(-)) states in the ODC-catalyzed decarboxylation of OMP [7].
• Uridine monophosphate (UMP) synthase is a bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC) [8].
• The COOH-terminal 258 amino acids of the human UMP synthase protein contain the orotidine-5'-monophosphate decarboxylase catalytic domain [9].
• The last two steps in the de novo biosynthesis of UMP are catalyzed by orotate phosphoribosyltransferase (OPRT; orotidine-5'-phosphate:pyrophosphate phosphoribosyltransferase; EC 2.4.2.10) and orotidine-5'-monophosphate decarboxylase (orotidine-5'-phosphate carboxy-lyase; EC 4.1.1.23) [9].

Chemical compound and disease context of Orotidine monophosphate

• Salmonella typhimurium orotate phosphoribosyltransferase (OPRTase) catalyzes the formation of orotidine 5'-monophosphate (OMP) from orotate and alpha-D-5-phosphoribosyl-1-pyrophosphate (PRPP) [10].

Biological context of Orotidine monophosphate

• Purification and characterization of yeast orotidine 5'-monophosphate decarboxylase overexpressed from plasmid PGU2 [11].
• The nucleotide sequence of the Myxococcus xanthus orotidine-5'-monophosphate decarboxylase (OMP DCase) gene was determined [3].
• Design of inhibitors of orotidine monophosphate decarboxylase using bioisosteric replacement and determination of inhibition kinetics [5].
• The 3-keto-L-gulonate 6-phosphate decarboxylase (KGPDC) encoded by the ulaD gene in the Escherichia coli genome [Yew, W. S., and Gerlt, J. A. (2002) J. Bacteriol. 184, 302-306] and orotidine 5'-monophosphate decarboxylase (OMPDC) are homologous (derived from a common ancestor) but catalyze different reactions [12].
• Evolution of enzymatic activities in the orotidine 5'-monophosphate decarboxylase suprafamily: crystallographic evidence for a proton relay system in the active site of 3-keto-L-gulonate 6-phosphate decarboxylase [13].

Anatomical context of Orotidine monophosphate

• This enzyme orotidine 5'-monophosphate phosphohydrolase (OMPase), was isolated from mouse liver microsomes as a separate entity from the nonspecific 5'-Nase [14].
• Following azaribine therapy there was a coordinate rise of the specific activities of erythrocyte orotate phosphoribosyltransferase and orotidine-5'-monophosphate decarboxylase [15].

Associations of Orotidine monophosphate with other chemical compounds

• The crystal structures of the enzyme orotidine-5'-monophosphate decarboxylase from Methanobacterium thermoautotrophicum complexed with its product UMP and the inhibitors 6-hydroxyuridine 5'-phosphate (BMP), XMP, and CMP are reported [16].
• The expressed ODCase domain has a lower affinity for the substrate orotidine 5'-monophosphate and the inhibitor 6-azauridine 5'-monophosphate than intact UMP synthase or an ODCase domain isolated after proteolysis of homogenous UMP synthase [17].
• The mechanism of orotidine 5'-monophosphate decarboxylase was studied computationally by using the decarboxylation of orotic acid analogues as model systems [18].
• Decarboxylation of orotidine 5'-monophosphate (Omp) to uridine 5'-monophosphate by orotidine 5'-monophosphate decarboxylase (ODCase) is currently the object of vivid debate [19].
• Orotate phosphoribosyltransferase (OPRTase; EC 2.4.2.10) catalyzes phosphoribosyl group transfer between alpha-D-5-phosphoribosyl-1-pyrophosphate and orotate to form orotidine-5'-monophosphate and pyrophosphate, the nucleotide-forming step in pyrimidine biosynthesis [20].

Gene context of Orotidine monophosphate

• Study of the kinetic and physical properties of the orotidine-5'-monophosphate decarboxylase domain from mouse UMP synthase produced in Saccharomyces cerevisiae [17].
• Sequence analysis of the URA1 gene encoding orotidine-5'-monophosphate decarboxylase of Schizophyllum commune [21].
• Two of the genes are the well-known pyr genes pyrDb and pyrF, encoding dihydroorotate dehydrogenase and orotidine monophosphate decarboxylase, respectively [22].
• A part of the pyrimidine biosynthetic operon including genes for orotate phosphoribosyltransferase (pyrE) and for orotidine-5'-monophosphate decarboxylase (pyrF) was cloned and sequenced [23].
• First, under the condition of equivalent mass concentrations of OPRTase and HGPRTase, the initial rate of orotidine monophosphate synthesis and the equilibrium state were greatly affected by the presence of HGPRTase activity [24].

Analytical, diagnostic and therapeutic context of Orotidine monophosphate

• The three-dimensional structures of orotidine 5'-monophosphate decarboxylases from four different organisms have been determined by X-ray crystallography [25].
• Purification, crystallization and preliminary X-ray study of orotidine 5'-monophosphate decarboxylase [26].
• A genomic clone encoding the Paracoccidioides brasiliensis orotidine monophosphate decarboxylase gene (PbrURA3) was isolated by screening a subgenomic plasmid DNA library of this fungus, using a PCR amplification product of the gene as a probe [27].
• Substrates (orotate for OPRTase or orotidine 5'-monophosphate for ODCase) and a product (UMP) of the enzymatic assay were separated by high-performance liquid chromatography (HPLC) using a reversed-phase column and an ion-pairing system; the amount of UMP was quantified by dual-wavelength uv detection at 260 and 278 nm [28].
• Elution with 2 X 5 ml of 0.1 M sodium chloride in 5 mM ammonium acetate removes all of the orotate and leaves all of the product orotidine monophosphate (OMP) bound so that it may be measured in a scintillation counter [29].

References