Uridine 5'-monophosphate synthase

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Revision as of 10:04, 23 March 2020

spinqualitylabelsall models Human uridine 5-monophosphate synthase OPD subunit dimer complex with UMP 2qcd Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Function Uridine 5’-monophosphate synthase (UMPS) is a bifunctional enzyme which catalyzes the formation of uridine monophosphate (UMP)[1]. UMPS N-terminal domain is an orotate phosphoribosyltransferase (OPRT) subunit which catalyzes the addition of ribose-phosphate to orotate forming orotidine 5’-monophosphate (OMP). The C-terminal subunit is orotidine 5’-phosphate decarboxylase (OPD) or OMP decarboxylase which decarboxylates OMP to form UMP. Potent inhibitors of OPD are BMP – a barbituric acid derivative and xanthosine-5'-monophosphate (XMP). Disease Defects in UMPS result in the hereditary rare metabolic disease orotic aciduria[2]. UMPS deficiency in Holstein cattle results in an autosomal disorder which causes early embryonic death of offspring[3]. Structural highlights in its [4] (the surface of chain B doesn't shown). Water molecules are shown as red spheres.

3D structures of uridine 5'-monophosphate synthase

Updated on 23-March-2020

References

1. ↑ Yablonski MJ, Pasek DA, Han BD, Jones ME, Traut TW. Intrinsic activity and stability of bifunctional human UMP synthase and its two separate catalytic domains, orotate phosphoribosyltransferase and orotidine-5'-phosphate decarboxylase. J Biol Chem. 1996 May 3;271(18):10704-8. PMID:8631878
2. ↑ Grohmann K, Lauffer H, Lauenstein P, Hoffmann GF, Seidlitz G. Hereditary orotic aciduria with epilepsy and without megaloblastic anemia. Neuropediatrics. 2015 Apr;46(2):123-5. doi: 10.1055/s-0035-1547341. Epub 2015 Mar, 10. PMID:25757096 doi:http://dx.doi.org/10.1055/s-0035-1547341
3. ↑ Schwenger B, Schober S, Simon D. DUMPS cattle carry a point mutation in the uridine monophosphate synthase gene. Genomics. 1993 Apr;16(1):241-4. PMID:8486364 doi:http://dx.doi.org/10.1006/geno.1993.1165
4. ↑ Wittmann JG, Heinrich D, Gasow K, Frey A, Diederichsen U, Rudolph MG. Structures of the human orotidine-5'-monophosphate decarboxylase support a covalent mechanism and provide a framework for drug design. Structure. 2008 Jan;16(1):82-92. PMID:18184586 doi:http://dx.doi.org/10.1016/j.str.2007.10.020