Uridine 5'-monophosphate synthase: Difference between revisions
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<StructureSection load='' size='350' side='right' caption='Human uridine 5-monophosphate synthase OPD subunit dimer complex with UMP [[2qcd]]' scene='52/526172/Cv/1' pspeed='8'> | |||
== Function == | |||
'''Uridine 5’-monophosphate synthase''' (UMPS) is a bifunctional enzyme which catalyzes the formation of uridine monophosphate (UMP)<ref>PMID:8631878</ref>. 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<ref>PMID:25757096</ref>. UMPS deficiency in Holstein cattle results in an autosomal disorder which causes early embryonic death of offspring<ref>PMID:8486364</ref>. | |||
== | == Structural highlights == | ||
<scene name='52/526172/Cv/8'>UMPS contains UMP</scene> in its <scene name='52/526172/Cv/9'>nucleotide-binding pocket</scene><ref>PMID:18184586</ref> (the surface of chain B doesn't shown). Water molecules are shown as red spheres. | |||
= | ==3D structures of uridine 5'-monophosphate synthase== | ||
[[Uridine 5'-monophosphate synthase 3D structures]] | |||
</StructureSection> | |||
== | |||
[[ | |||
==References== | |||
<references /> | |||
[[Category:Topic Page]] | [[Category:Topic Page]] | ||
Latest revision as of 12:24, 7 January 2021
FunctionUridine 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). DiseaseDefects 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 highlightsin its [4] (the surface of chain B doesn't shown). Water molecules are shown as red spheres. 3D structures of uridine 5'-monophosphate synthase |
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ReferencesReferences
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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