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. | '''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. Potent inhibitors of OPD are BMP – a barbituric acid derivative and xanthosine-5'-monophosphate (XMP). | ||
== Disease == | == Disease == | ||
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**[[3qw3]] – LdOPD – ''Leishmania donovani'' <br /> | **[[3qw3]] – LdOPD – ''Leishmania donovani'' <br /> | ||
**[[2za2]] - PfOPD - ''Plasmodium falciparum''<br /> | **[[2za2]] - PfOPD - ''Plasmodium falciparum''<br /> | ||
**[[1l2u]] - | **[[1l2u]] - EcOPD - ''Escherichia coli''<br /> | ||
**[[2cz5]], [[2czd]] - PhOPD - ''Pyrococcus horikoshii''<br /> | |||
**[[3tfx]] - OPD - ''Lactobacillus acidophilus''<br /> | |||
**[[3tr2]] - OPD - ''Coxiella burnetii''<br /> | |||
**[[3r89]] - OPD - ''Anaerococcus prevorii''<br /> | |||
**[[3v75]] - OPD - ''Streptomyces avermitilis''<br /> | |||
**[[1vqt]] - OPD - ''Thermotoga maritima''<br /> | |||
**[[3ldv]] - VcOPD - ''Vibrio cholerae''<br /> | |||
**[[3ru6]] - OPD - ''Campylobacter jejuni''<br /> | |||
**[[2yyt]], [[2yyu]] - OPD - ''Geobacillus kaustophilus''<br /> | |||
**[[3g18]], [[3g1s]], [[3g1y]], [[3m41]], [[3m43]], [[3m44]], [[3m47]], [[3m5x]], [[3m5y]], [[3m5z]] – MtOPD (mutant) – ''Methanothermobacter thermautotrophicus''<br /> | |||
*Uridine 5’-monophosphate synthase OPD subunit complex | *Uridine 5’-monophosphate synthase OPD subunit complex with reactants | ||
**[[2v30]], [[2qcd]] - hOPD + UMP<br /> | **[[2v30]], [[2qcd]], [[2qcn]] - hOPD + UMP<br /> | ||
**[[3ewy]] - hOPD (mutant) + 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 /> | **[[2qcg]], [[2qch]], [[3bgg]], [[3bgj]], [[3bk0]], [[3g3d]], [[3g3m]], [[3ewz]], [[3ex2]], [[3ex3]], [[3ex4]], [[3dbp]], [[3l0k]], [[3l0n]], [[3mo7]], [[3mw7]] - hOPD + UMP derivative<br /> | ||
**[[2qcf]], [[2qcm]], [[2qcn]], [[3ewu]], [[3ewx]], [[3ex6]] - hOPD (mutant) + UMP derivative<br /> | **[[2qcf]], [[2qcm]], [[2qcn]], [[3ewu]], [[3ewx]], [[3ex6]] - hOPD (mutant) + UMP derivative<br /> | ||
**[[2qcl]] - hOPD (mutant) + OMP<br /> | **[[2qcl]] - hOPD (mutant) + OMP<br /> | ||
**[[3ex1]] - hOPD + UMP derivative + UMP<br /> | **[[3ex1]] - hOPD + UMP derivative + UMP<br /> | ||
**[[2qcl]] - yOPD (mutant) + OMP <br /> | **[[2qcl]] - yOPD (mutant) + OMP <br /> | ||
**[[3gdl]] - yOPD + UMP derivative<br /> | **[[3gdl]] - yOPD + UMP derivative<br /> | ||
**[[1dqx]], [[3gdt]] - yOPD (mutant) + UMP derivative<br /> | **[[1dqx]], [[3gdt]] - yOPD (mutant) + UMP derivative<br /> | ||
**[[ | **[[4o8r]], [[4o11]], [[4nx5]], [[4nt0]], [[4nuw]], [[3wjw]], [[3wjx]], [[3wjy]], [[3wjz]], [[3w07]], [[3sgu]], [[3ssj]], [[3sw6]], [[3thq]], [[3wjw]], [[3wjx], [[3w07]]] - MtOPD + UMP derivative<br /> | ||
**[[1km1]], [[1km2]], [[1km3]], [[1km4]], [[1km5]], [[1kly]], [[1klz]], [[1km0]], [[1los]], [[2zz2]], [[2zz3]], [[2zz4]], [[2zz5]], [[2zz6]], [[2zz7]], [[3g1a]], [[3g1d]], [[3g1v]], [[3g1x]], [[3g22]], [[3g24]], [[3lld]], [[3llf]], [[3nq6]], [[3pbu]], [[3pbv]], [[3pbw]], [[3pby]], [[3pc0]], [[3sy5]], [[3wjy]], [[3wjz]], [[2e6y]] - MtOPD (mutant) + UMP derivative<br /> | |||
**[[1km1]], [[1kly]], [[1klz]], [[1km0]] - MtOPD (mutant) + UMP derivative<br /> | |||
**[[3wk0]], [[3wk1]], [[3wk2]], [[3wk3]] - MtOPD + OMP derivative<br /> | **[[3wk0]], [[3wk1]], [[3wk2]], [[3wk3]] - MtOPD + OMP derivative<br /> | ||
**[[1km6]] - MtOPD (mutant) + OMP <br /> | **[[1km6]], [[3g1f]], [[3g1h]] - MtOPD (mutant) + OMP derivative <br /> | ||
**[[2za3]] - PfOPD + UMP <br /> | |||
**[[1lp6]] - ArOPD + CMP - ''Archaea''<br /> | |||
**[[1loq]] - ArOPD + UMP <br /> | |||
**[[3uwq]] - VcOPD + UMP <br /> | |||
**[[2cze]] - PhOPD + UMP <br /> | |||
*Uridine 5’-monophosphate synthase OPD subunit complex with inhibitor | |||
**[[3mi2]], [[4hib]], [[4hkp]] - hOPD + inhibitor<br /> | |||
**[[3bvj]] - hOPD + XMP<br /> | |||
**[[4lw7]], [[3ltp]], [[4luj]], [[1lor]] – MtOPD + BMP <br /> | |||
**[[4lc6]], [[4lc8]], [[4fx8]], [[4gc4]], [[4fx6]], [[4fxr]], [[3v1p]], [[1x1z]], [[3lht]], [[3lhu]], [[3lhv]], [[3lhw]], [[3lhy]], [[3lhz]], [[3li0]], [[3li1]], [[3lts]], [[3lty]], [[3lv5]], [[3lv6]], [[3m1z]], [[3nq7]], [[3nqa]], [[3nqc]], [[3nqd]], [[3nqe]], [[3nqf]], [[3nqg]], [[3nqm]], [[3p5y]], [[3p5z]], [[3p60]], [[3p61]], [[3qez]], [[3qf0]], [[3qmr]], [[3qms]], [[3qmt]], [[3rlu]], [[3rlv]], [[3siz]], [[3sj3]], [[3v1p]], [[4lw7]], [[2zz1]] – MtOPD (mutant) + BMP <br /> | |||
**[[1lol]] - MtOPD + XMP <br /> | **[[1lol]] - MtOPD + XMP <br /> | ||
**[[3sec]] - MtOPD + inhibitor<br /> | |||
**[[2czf]] - PhOPD + XMP<br /> | |||
**[[4muz]] – AfOPD + BMP <br /> | **[[4muz]] – AfOPD + BMP <br /> | ||
**[[4luj]] – MjOPD + BMP <br /> | **[[4luj]] – MjOPD + BMP <br /> | ||
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**[[4dbe]] – SsOPD + BMP <br /> | **[[4dbe]] – SsOPD + BMP <br /> | ||
**[[3ve7]] – MsOPD + BMP <br /> | **[[3ve7]] – MsOPD + BMP <br /> | ||
**[[1jjk]] – EcOPD + BMP <br /> | |||
**[[3vi2]] - PfOPD + inhibitor<br /> | **[[3vi2]] - PfOPD + inhibitor<br /> | ||
**[[2za1]] - PfOPD + OMP <br /> | **[[2za1]] - PfOPD + OMP <br /> | ||
**[[ | **[[1dqx]] – yOPD (mutant) + BMP <br /> | ||
*Uridine 5’-monophosphate synthase OPRT subunit see orotate phosphoribosyltransferase in [[Phosphoribosyltransferase]] | *Uridine 5’-monophosphate synthase OPRT subunit see orotate phosphoribosyltransferase in [[Phosphoribosyltransferase]] | ||
Revision as of 20:36, 5 October 2018
FunctionUridine 5’-monophosphate synthase (UMPS) is a bifunctional enzyme 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 shown as red spheres. |
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3D structures of uridine 5'-monophosphate synthase3D structures of uridine 5'-monophosphate synthase
Updated on 05-October-2018 {{#tree:id=OrganizedByTopic|openlevels=0|
- Uridine 5’-monophosphate synthase OMP decarboxylase subunit
- 3gdk - yOPD – yeast
- 1dqw, 3gdr, 3gdm – yOPD (mutant)
- 2eaw, 2jgy, 2p1f, 2qcc, 2qce - hOPD – human
- 4n2y – AfOPD – Archaeoglobus fulgidus
- 4lui – MjOPD – Methanocaldococcus jannaschii
- 4dbd – SsOPD – Sulfolobus solftaricus
- 4df0 – TnOPD – Thermoproteus neutrophilus
- 3ve9 – MsOPD – Metallosphaera sedula
- 3qw3 – LdOPD – Leishmania donovani
- 2za2 - PfOPD - Plasmodium falciparum
- 1l2u - EcOPD - Escherichia coli
- 2cz5, 2czd - PhOPD - Pyrococcus horikoshii
- 3tfx - OPD - Lactobacillus acidophilus
- 3tr2 - OPD - Coxiella burnetii
- 3r89 - OPD - Anaerococcus prevorii
- 3v75 - OPD - Streptomyces avermitilis
- 1vqt - OPD - Thermotoga maritima
- 3ldv - VcOPD - Vibrio cholerae
- 3ru6 - OPD - Campylobacter jejuni
- 2yyt, 2yyu - OPD - Geobacillus kaustophilus
- 3g18, 3g1s, 3g1y, 3m41, 3m43, 3m44, 3m47, 3m5x, 3m5y, 3m5z – MtOPD (mutant) – Methanothermobacter thermautotrophicus
- 3gdk - yOPD – yeast
- Uridine 5’-monophosphate synthase OPD subunit complex with reactants
- 2v30, 2qcd, 2qcn - hOPD + UMP
- 3ewy - hOPD (mutant) + UMP
- 2qcg, 2qch, 3bgg, 3bgj, 3bk0, 3g3d, 3g3m, 3ewz, 3ex2, 3ex3, 3ex4, 3dbp, 3l0k, 3l0n, 3mo7, 3mw7 - hOPD + UMP derivative
- 2qcf, 2qcm, 2qcn, 3ewu, 3ewx, 3ex6 - hOPD (mutant) + UMP derivative
- 2qcl - hOPD (mutant) + OMP
- 3ex1 - hOPD + UMP derivative + UMP
- 2qcl - yOPD (mutant) + OMP
- 3gdl - yOPD + UMP derivative
- 1dqx, 3gdt - yOPD (mutant) + UMP derivative
- 4o8r, 4o11, 4nx5, 4nt0, 4nuw, 3wjw, 3wjx, 3wjy, 3wjz, 3w07, 3sgu, 3ssj, 3sw6, 3thq, 3wjw, [[3wjx], 3w07] - MtOPD + UMP derivative
- 1km1, 1km2, 1km3, 1km4, 1km5, 1kly, 1klz, 1km0, 1los, 2zz2, 2zz3, 2zz4, 2zz5, 2zz6, 2zz7, 3g1a, 3g1d, 3g1v, 3g1x, 3g22, 3g24, 3lld, 3llf, 3nq6, 3pbu, 3pbv, 3pbw, 3pby, 3pc0, 3sy5, 3wjy, 3wjz, 2e6y - MtOPD (mutant) + UMP derivative
- 3wk0, 3wk1, 3wk2, 3wk3 - MtOPD + OMP derivative
- 1km6, 3g1f, 3g1h - MtOPD (mutant) + OMP derivative
- 2za3 - PfOPD + UMP
- 1lp6 - ArOPD + CMP - Archaea
- 1loq - ArOPD + UMP
- 3uwq - VcOPD + UMP
- 2cze - PhOPD + UMP
- 2v30, 2qcd, 2qcn - hOPD + UMP
- Uridine 5’-monophosphate synthase OPD subunit complex with inhibitor
- 3mi2, 4hib, 4hkp - hOPD + inhibitor
- 3bvj - hOPD + XMP
- 4lw7, 3ltp, 4luj, 1lor – MtOPD + BMP
- 4lc6, 4lc8, 4fx8, 4gc4, 4fx6, 4fxr, 3v1p, 1x1z, 3lht, 3lhu, 3lhv, 3lhw, 3lhy, 3lhz, 3li0, 3li1, 3lts, 3lty, 3lv5, 3lv6, 3m1z, 3nq7, 3nqa, 3nqc, 3nqd, 3nqe, 3nqf, 3nqg, 3nqm, 3p5y, 3p5z, 3p60, 3p61, 3qez, 3qf0, 3qmr, 3qms, 3qmt, 3rlu, 3rlv, 3siz, 3sj3, 3v1p, 4lw7, 2zz1 – MtOPD (mutant) + BMP
- 1lol - MtOPD + XMP
- 3sec - MtOPD + inhibitor
- 2czf - PhOPD + XMP
- 4muz – AfOPD + BMP
- 4luj – MjOPD + BMP
- 4df1 – TnOPD + BMP
- 4dbe – SsOPD + BMP
- 3ve7 – MsOPD + BMP
- 1jjk – EcOPD + BMP
- 3vi2 - PfOPD + inhibitor
- 2za1 - PfOPD + OMP
- 1dqx – yOPD (mutant) + BMP
- 3mi2, 4hib, 4hkp - hOPD + inhibitor
- Uridine 5’-monophosphate synthase OPRT subunit see orotate phosphoribosyltransferase in Phosphoribosyltransferase
}}
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