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IntroductionIntroduction

Orotidine monophosphate decarboxylase (ODCase), also known as orotidine 5’-monophosphate decarboxylase (OMP decarboxylase) or orotidine 5’-phosphate decarboxylase is an enzyme involved in pyrimidine biosynthesis. It catalyzes the conversion of orotidine 5’-monophosphate (OMP) to uridine 5’-monophosphate (UMP). This reaction is the final step in de novo pyrimidine nucleotide synthesis and is an essential precursor for both DNA and RNA. The main structure of orotidine monophosphate decarboxylase is a TIM barrel, with one opening acting as the binding site, while the other side is closed-off. ODCase is often bound to other proteins in biological conditions. In single-cellular organisms, it can form a dimeric enzyme by binding to another ODCase^[1]. In multi-cellular organisms it can bind to orotate phosphoribosyltransferase to form a bifunctional protein, UMP synthase^[2]. Additionally this enzyme has been studied for it’s remarkable catalytic efficiency.^[3].

1dv7, resolution 1.80Å ()

Activity:

Orotidine-5'-phosphate decarboxylase, with EC number 4.1.1.23

Related:

1dvj

Structural annotation:
Resources:	CATH : 1Dv7A00 InterPro : Ipr011060, Ipr014732, Ipr001754, Ipr013785 Pfam : PF00215 SCOP : d1dv7a_ UniProt : O26232

Functional annotation:
Biological process:	pyrimidine nucleotide biosynthetic process 'de novo' pyrimidine base biosynthetic process metabolic process
Molecular function:	carboxy-lyase activity orotidine-5'-phosphate decarboxylase activity catalytic activity lyase activity

Evolutionary conservation:

Toggle Conservation Colors:
Further Information:	Caveats, Explanation, Complete Results at ConSurfDB

Resources:

FirstGlance, OCA, RCSB, PDBsum, TOPSAN

Coordinates:

save as pdb, mmCIF, xml

StructureStructure

Orotidine monophosphate decarboxylase has a TIM barrel structure^[1]^[3]. Like a typical TIM barrel, it is cylindrically-shaped as a result of parallel α helices and β sheets arranged in a circular manner. In biological conditions, ODCase is found in dimeric form, covalently bonded to a second ODCase^[3]. Each ODCase has 9 α helices that encompass 8 internal β sheets^[1]^[3]. The both the C and N terminus are oriented on the same side of the monomer and directed away from the interface between the two monomers; this could explain how the enzymes can still maintain functionality when bound to another protein^[3]. The loops connecting these (alpha) helices and (beta) sheets are where the active sites are found^[3]. The active site is only found on one side of the barrel, the “open” side, while the other side is closed off^[3].

Active SiteActive Site

(to be expanded later; discussion of alternating charges: Lys-Asp-Lys-Asp, ligand binding, etc.)

FunctionFunction

(to be expanded later; discussion of decarboxylase reaction, including mechanism & biological significance)

UMP SynthaseUMP Synthase

In multicellular eukaryotes, orotidine monophosphate decarboxylase associates with orotate phosphoribosyltransferase to form a bifunctional protein, uridine monophosphate synthase (UMP Synthase)^[4]^[2]. UMP synthase carries out the last two steps in pyrimidine biosynthesis, converting orotate to uridine 5'-monophosphate^[2]. This reaction involves first adding ribose-P to orotate to form orotidine 5'-monophosphate, followed by a decarboxylation reaction to form uridine 5'-monophosphate^[2]. In microorganisms these two enzymes are separate and coded by distinct genes. However research has shown that all multicellular eukaryotes so far code the genes for these two enzymes together and as a result they are covalently bonded as a bifunctional protein with two distinct catalytic domains^[2].

Rate of CatalysisRate of Catalysis

(to be expanded later; discussion of how amazingly efficient this reaction is: 78 million years for spontaneous reaction compared with 18 milliseconds with catalyst; also that it functions without metals or cofactors)

Substrate DestabilizationSubstrate Destabilization

(to be expanded later; discussion of how the enzyme amazing catalytic rate is achieved by destabilizing the substrate reactive group & how this is compensated with binding the phosphate and ribose groups)

^[4]

ReferencesReferences

↑ ^1.0 ^1.1 ^1.2 Wu N, Mo Y, Gao J, Pai EF. Electrostatic stress in catalysis: structure and mechanism of the enzyme orotidine monophosphate decarboxylase. Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2017-22. PMID:10681441 doi:10.1073/pnas.050417797
↑ ^2.0 ^2.1 ^2.2 ^2.3 ^2.4 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
↑ ^3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 ^3.6 Miller BG, Hassell AM, Wolfenden R, Milburn MV, Short SA. Anatomy of a proficient enzyme: the structure of orotidine 5'-monophosphate decarboxylase in the presence and absence of a potential transition state analog. Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2011-6. PMID:10681417 doi:10.1073/pnas.030409797
↑ ^4.0 ^4.1 Lee JK, Houk KN. A proficient enzyme revisited: the predicted mechanism for orotidine monophosphate decarboxylase. Science. 1997 May 9;276(5314):942-5. PMID:9139656

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA, Sarah Geisheimer

[Wu-1] 1.0 ^1.1 ^1.2 Wu N, Mo Y, Gao J, Pai EF. Electrostatic stress in catalysis: structure and mechanism of the enzyme orotidine monophosphate decarboxylase. Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2017-22. PMID:10681441 doi:10.1073/pnas.050417797

[Yablonski-2] 2.0 ^2.1 ^2.2 ^2.3 ^2.4 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

[Miller-3] 3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 ^3.6 Miller BG, Hassell AM, Wolfenden R, Milburn MV, Short SA. Anatomy of a proficient enzyme: the structure of orotidine 5'-monophosphate decarboxylase in the presence and absence of a potential transition state analog. Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2011-6. PMID:10681417 doi:10.1073/pnas.030409797

[Lee-4] 4.0 ^4.1 Lee JK, Houk KN. A proficient enzyme revisited: the predicted mechanism for orotidine monophosphate decarboxylase. Science. 1997 May 9;276(5314):942-5. PMID:9139656

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