Human malaria parasite orotate phosphoribosyltransferase: functional expression, characterization of kinetic reaction mechanism and inhibition profile

A Mycobacterial Phosphoribosyltransferase Promotes Bacillary Survival by Inhibiting Oxidative Stress and Autophagy Pathways in Macrophages and Zebrafish

“…Similarly, in our study, the complementation of mimG with the Rv3242c restored the virulence defect of the mimG mutant, indicating that the two genes are functionally conserved. These results are also in agreement with previous observations that deletion of PRT leads to impaired survival in M. tuberculosis (26) and severely compromises the infection process of parasites (91). Although the strong binding affinity of Rv3242c with ConA suggested the presence of a mannose sugar in Rv3242c, it remains to be demonstrated experimentally whether Rv3242c and mimG indeed contain mannosylated residues.…”

“…Key enzymes in this pathway are several phosphoribosyltransferases. Previously, de novo pyrimidine biosynthesis has been shown to be required for cell invasion and virulence of parasites (90,91), in which disruption of this pathway led to an avirulent phenotype. Although the metabolism required for sustaining mycobacterial survival during latency is still poorly understood, experimental evidence has suggested the essentiality of nucleotide synthesis in latent bacilli (92).…”

Expression of Functional Plasmodium falciparum Enzymes Using a Wheat Germ Cell-Free System

“…Attachment of a phosphoribose from phosphoribosylpyrophosphate (PRPP) to orotic acid can be monitored by direct increases in absorption at 295 nm (15). To a 500-l reaction mixture containing 50 mM Tris-HCl buffer, pH 8.0, 2 mM ␤-mercaptoethanol, 5 mM MgCl 2 , 0.4 mM OMP, and 1 mM pyrophosphate, various quantities of orotate phosphoribosyl transferase (OPRT)-or GFP-translated lysate were added.…”

“…These explanations include the high AT content of the malaria coding regions, internal start and stop sites, autologous feedback loops, and nonspecific nucleic acid binding (6,12,13). Efforts to overcome these potential issues, using tRNA augmentation, optimized codons, and alteration of host expression, have led to occasional successes (7,(12)(13)(14)(15)(16)(17)(18) but no universal malaria protein expression strategy.…”

Malaria parasite carbonic anhydrase: inhibition of aromatic/heterocyclic sulfonamides and its therapeutic potential

“…It salvages the preformed purine bases/nucleosides from the human host and converts them to their mono-, di-and triphosphates. The parasite can only synthesize pyrimidines de novo from HCO 3 -, ATP, glutamine, aspartate, and 5-phosphoribosyl-1-pyrophosphate [43][44][45][46][47][48][49][50][51][52][53] . These unique properties on both purine and pyrimidine requirement of the parasite are key differences from the human host, in which both functional de novo and salvage pathways of the purine and pyrimidine synthesis exists [46,48,[54][55][56][57][58].…”