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'>
<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 ==
== Function ==
'''Uridine 5’-monophosphate synthase''' (UMPS) is a bifunctional enzyme 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. A potent inhibitor of OPD is BMP – a barbituric acid derivative.
'''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 ==  
== Disease ==  
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== Structural highlights ==
== Structural highlights ==
<scene name='52/526172/Cv/6'>UMPS contains UMP</scene> in its <scene name='52/526172/Cv/7'>nucleotide-binding pocket</scene><ref>PMID:18184586</ref> (the surface of chain B doesn't shown). Water molecules shown as red spheres.
<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>
</StructureSection>
==3D structures of uridine 5'-monophosphate synthase==
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|
*Uridine 5’-monophosphate synthase OMP decarboxylase subunit
**[[3gdk]] - yOPD – yeast<br />
**[[1dqw]], [[3gdr]], [[3gdm]] – yOPD (mutant) <br />
**[[2eaw]], [[2jgy]], [[2p1f]], [[2qcc]], [[2qce]] - hOPD – human<br />
**[[4n2y]] – AfOPD – ''Archaeoglobus fulgidus''<br />
**[[4lui]] – MjOPD – ''Methanocaldococcus jannaschii''<br />
**[[4dbd]] – SsOPD – ''Sulfolobus solftaricus'' <br />
**[[4df0]] – TnOPD – ''Thermoproteus neutrophilus'' <br />
**[[3ve9]] – MsOPD – ''Metallosphaera sedula'' <br />
**[[3qw3]] – LdOPD – ''Leishmania donovani'' <br />
**[[2za2]] - PfOPD - ''Plasmodium falciparum''<br />
**[[1l2u]] - OPD - ''Escherichia coli''<br />
*Uridine 5’-monophosphate synthase OPD subunit complex
**[[2v30]], [[2qcd]] - hOPD + UMP<br />
**[[3ewy]] - hOPD (mutant) + UMP<br />
**[[2qcg]], [[2qch]], [[3bgg]], [[3bgj]], [[3bk0]], [[3g3d]], [[3g3m]], [[3ewz]], [[3ex2]], [[3ex3]], [[3ex4]], [[3dbp]], [[3l0k]], [[3l0n]], [[3mo7]], [[3mw7]] - hOPD + UMP derivative<br />
**[[3bvj]] - hOPD + xanthosine 5’-monophosphate<br />
**[[2qcf]], [[2qcm]], [[2qcn]], [[3ewu]], [[3ewx]], [[3ex6]] - hOPD (mutant) + UMP derivative<br />
**[[2qcl]] - hOPD (mutant) + OMP<br />
**[[3mi2]], [[4hib]], [[4hkp]] - hOPD + inhibitor<br />
**[[3ex1]] - hOPD + UMP derivative + UMP<br />
**[[2qcl]] - yOPD (mutant) + OMP <br />
**[[3gdl]] - yOPD + UMP derivative<br />
**[[1dqx]], [[3gdt]] - yOPD (mutant) + UMP derivative<br />
**[[4lw7]] – MtOPD + BMP – ''Methanothermobacter thermautotrophicus''<br />
**[[4lc6]], [[4lc8]], [[4fx8]], [[4gc4]], [[4fx6]], [[4fxr]], [[3v1p]] – MtOPD (mutant) + BMP <br />
**[[4o8r]], [[4o11]], [[4nx5]], [[4nt0]], [[4nuw]], [[3wjw]], [[3wjx]], [[3wjy]], [[3wjz]], [[3w07]] - MtOPD + UMP derivative<br />
**[[1km1]], [[1kly]], [[1klz]], [[1km0]] - MtOPD (mutant) + UMP derivative<br />
**[[3wk0]], [[3wk1]], [[3wk2]], [[3wk3]] - MtOPD + OMP derivative<br />
**[[1km6]] - MtOPD (mutant) + OMP <br />
**[[1lol]] - MtOPD + XMP <br />
**[[4muz]] – AfOPD + BMP <br />
**[[4luj]] – MjOPD + BMP <br />
**[[4df1]] – TnOPD + BMP <br />
**[[4dbe]] – SsOPD + BMP <br />
**[[3ve7]] – MsOPD + BMP <br />
**[[3vi2]] - PfOPD + inhibitor<br />
**[[2za1]] - PfOPD + OMP <br />
**[[2za3]] - PfOPD + UMP <br />
**[[1lp6]] - ArOPD + CMP - ''Archaea''<br />
**[[1loq]] - ArOPD + UMP <br />
*Uridine 5’-monophosphate synthase OPRT subunit see orotate phosphoribosyltransferase in [[Phosphoribosyltransferase]]


}}
==References==
==References==
<references />
<references />
[[Category:Topic Page]]
[[Category:Topic Page]]

Latest revision as of 12:24, 7 January 2021

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

Uridine 5'-monophosphate synthase 3D structures

Human uridine 5-monophosphate synthase OPD subunit dimer complex with UMP 2qcd

Drag the structure with the mouse to rotate

ReferencesReferences

  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

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Michal Harel, Alexander Berchansky, Joel L. Sussman
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