PDBsum entry 1eix

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Lyase PDB id
Protein chains
231 a.a. *
BMQ ×4
Waters ×379
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Structure of orotidine 5'-monophosphate decarboxylase from e. Coli, co-crystallised with the inhibitor bmp
Structure: Orotidine 5'-monophosphate decarboxylase. Chain: a, b, c, d. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
2.50Å     R-factor:   0.191     R-free:   0.264
Authors: P.Harris,J.C.N.Poulsen,K.F.Jensen,S.Larsen
Key ref:
P.Harris et al. (2000). Structural basis for the catalytic mechanism of a proficient enzyme: orotidine 5'-monophosphate decarboxylase. Biochemistry, 39, 4217-4224. PubMed id: 10757968 DOI: 10.1021/bi992952r
29-Feb-00     Release date:   15-Mar-00    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P08244  (PYRF_ECOLI) -  Orotidine 5'-phosphate decarboxylase
245 a.a.
231 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Orotidine-5'-phosphate decarboxylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Pyrimidine Biosynthesis
      Reaction: Orotidine 5'-phosphate = UMP + CO2
Orotidine 5'-phosphate
Bound ligand (Het Group name = BMQ)
matches with 95.00% similarity
+ CO(2)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     5 terms  


DOI no: 10.1021/bi992952r Biochemistry 39:4217-4224 (2000)
PubMed id: 10757968  
Structural basis for the catalytic mechanism of a proficient enzyme: orotidine 5'-monophosphate decarboxylase.
P.Harris, J.C.Navarro Poulsen, K.F.Jensen, S.Larsen.
Orotidine 5'-monophosphate decarboxylase (ODCase) catalyzes the decarboxylation of orotidine 5'-monophosphate, the last step in the de novo synthesis of uridine 5'-monophosphate. ODCase is a very proficient enzyme [Radzicka, A., and Wolfenden, R. (1995) Science 267, 90-93], enhancing the reaction rate by a factor of 10(17). This proficiency has been enigmatic, since it is achieved without metal ions or cofactors. Here we present a 2.5 A resolution structure of ODCase complexed with the inhibitor 1-(5'-phospho-beta-D-ribofuranosyl)barbituric acid. It shows a closely packed dimer composed of two alpha/beta-barrels with two shared active sites. The orientation of the orotate moiety of the substrate is unambiguously deduced from the structure, and previously proposed catalytic mechanisms involving protonation of O2 or O4 can be ruled out. The proximity of the OMP carboxylate group with Asp71 appears to be instrumental for the decarboxylation of OMP, either through charge repulsion or through the formation of a very short O.H.O hydrogen bond between the two carboxylate groups.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20424759 S.Thirumalairajan, B.Mahaney, and S.L.Bearne (2010).
Interrogation of the active site of OMP decarboxylase from Escherichia coli with a substrate analogue bearing an anionic group at C6.
  Chem Commun (Camb), 46, 3158-3160.  
20047306 Z.Bello, and C.Grubmeyer (2010).
Roles for cationic residues at the quinolinic acid binding site of quinolinate phosphoribosyltransferase.
  Biochemistry, 49, 1388-1395.  
19349645 A.Jakubowska, and R.Korona (2009).
Lack of evolutionary conservation at positions important for thermal stability in the yeast ODCase protein.
  Mol Biol Evol, 26, 1431-1434.  
19435313 B.M.Wood, K.K.Chan, T.L.Amyes, J.P.Richard, and J.A.Gerlt (2009).
Mechanism of the orotidine 5'-monophosphate decarboxylase-catalyzed reaction: effect of solvent viscosity on kinetic constants.
  Biochemistry, 48, 5510-5517.  
19435314 K.K.Chan, B.M.Wood, A.A.Fedorov, E.V.Fedorov, H.J.Imker, T.L.Amyes, J.P.Richard, S.C.Almo, and J.A.Gerlt (2009).
Mechanism of the orotidine 5'-monophosphate decarboxylase-catalyzed reaction: evidence for substrate destabilization.
  Biochemistry, 48, 5518-5531.
PDB codes: 3g18 3g1a 3g1d 3g1f 3g1h 3g1s 3g1v 3g1x 3g1y 3g22 3g24 3gdk 3gdl 3gdr 3gdt
19618917 K.Toth, T.L.Amyes, B.M.Wood, K.K.Chan, J.A.Gerlt, and J.P.Richard (2009).
An examination of the relationship between active site loop size and thermodynamic activation parameters for orotidine 5'-monophosphate decarboxylase from mesophilic and thermophilic organisms.
  Biochemistry, 48, 8006-8013.  
18184586 J.G.Wittmann, D.Heinrich, K.Gasow, A.Frey, U.Diederichsen, and M.G.Rudolph (2008).
Structures of the human orotidine-5'-monophosphate decarboxylase support a covalent mechanism and provide a framework for drug design.
  Structure, 16, 82-92.
PDB codes: 2qcc 2qcd 2qce 2qcf 2qcg 2qch 2qcl 2qcm 2qcn
18598058 S.A.Barnett, T.L.Amyes, B.M.Wood, J.A.Gerlt, and J.P.Richard (2008).
Dissecting the total transition state stabilization provided by amino acid side chains at orotidine 5'-monophosphate decarboxylase: a two-part substrate approach.
  Biochemistry, 47, 7785-7787.  
19039361 W.O.Wepukhulu, V.L.Smiley, B.Vemulapalli, J.A.Smiley, L.M.Phillips, and J.K.Lee (2008).
A substantial oxygen isotope effect at O2 in the OMP decarboxylase reaction: mechanistic implications.
  Org Biomol Chem, 6, 4533-4541.  
17967036 C.A.Lewis, and R.Wolfenden (2007).
Indiscriminate binding by orotidine 5'-phosphate decarboxylase of uridine 5'-phosphate derivatives with bulky anionic c6 substituents.
  Biochemistry, 46, 13331-13343.  
  16754976 S.R.Krungkrai, K.Tokuoka, Y.Kusakari, T.Inoue, H.Adachi, H.Matsumura, K.Takano, S.Murakami, Y.Mori, Y.Kai, J.Krungkrai, and T.Horii (2006).
Crystallization and preliminary crystallographic analysis of orotidine 5'-monophosphate decarboxylase from the human malaria parasite Plasmodium falciparum.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 542-545.  
14567674 E.L.Wise, W.S.Yew, J.A.Gerlt, and I.Rayment (2003).
Structural evidence for a 1,2-enediolate intermediate in the reaction catalyzed by 3-keto-L-gulonate 6-phosphate decarboxylase, a member of the orotidine 5'-monophosphate decarboxylase suprafamily.
  Biochemistry, 42, 12133-12142.
PDB codes: 1q6l 1q6o 1q6q 1q6r
12045113 B.G.Miller, and R.Wolfenden (2002).
Catalytic proficiency: the unusual case of OMP decarboxylase.
  Annu Rev Biochem, 71, 847-885.  
11900527 E.Wise, W.S.Yew, P.C.Babbitt, J.A.Gerlt, and I.Rayment (2002).
Homologous (beta/alpha)8-barrel enzymes that catalyze unrelated reactions: orotidine 5'-monophosphate decarboxylase and 3-keto-L-gulonate 6-phosphate decarboxylase.
  Biochemistry, 41, 3861-3869.
PDB codes: 1kv8 1kw1
11876660 H.Cao, B.L.Pietrak, and C.Grubmeyer (2002).
Quinolinate phosphoribosyltransferase: kinetic mechanism for a type II PRTase.
  Biochemistry, 41, 3520-3528.  
12216739 M.A.Kurinovich, and J.K.Lee (2002).
The acidity of uracil and uracil analogs in the gas phase: four surprisingly acidic sites and biological implications.
  J Am Soc Mass Spectrom, 13, 985-995.  
12011084 N.Wu, and E.F.Pai (2002).
Crystal structures of inhibitor complexes reveal an alternate binding mode in orotidine-5'-monophosphate decarboxylase.
  J Biol Chem, 277, 28080-28087.
PDB codes: 1lol 1loq 1lor 1los 1lp6
11900543 N.Wu, W.Gillon, and E.F.Pai (2002).
Mapping the active site-ligand interactions of orotidine 5'-monophosphate decarboxylase by crystallography.
  Biochemistry, 41, 4002-4011.
PDB codes: 1kly 1klz 1km0 1km1 1km2 1km3 1km4 1km5 1km6
12107279 S.Hur, and T.C.Bruice (2002).
Molecular dynamic study of orotidine-5'-monophosphate decarboxylase in ground state and in intermediate state: a role of the 203-218 loop dynamics.
  Proc Natl Acad Sci U S A, 99, 9668-9673.  
11828433 A.Warshel, J.Florián, M.Strajbl, and J.Villà (2001).
Circe effect versus enzyme preorganization: what can be learned from the structure of the most proficient enzyme?
  Chembiochem, 2, 109-111.  
11371183 B.G.Miller, G.L.Butterfoss, S.A.Short, and R.Wolfenden (2001).
Role of enzyme-ribofuranosyl contacts in the ground state and transition state for orotidine 5'-phosphate decarboxylase: a role for substrate destabilization?
  Biochemistry, 40, 6227-6232.  
11395407 J.A.Gerlt, and P.C.Babbitt (2001).
Divergent evolution of enzymatic function: mechanistically diverse superfamilies and functionally distinct suprafamilies.
  Annu Rev Biochem, 70, 209-246.  
11526316 J.C.Poulsen, P.Harris, K.F.Jensen, and S.Larsen (2001).
Selenomethionine substitution of orotidine-5'-monophosphate decarboxylase causes a change in crystal contacts and space group.
  Acta Crystallogr D Biol Crystallogr, 57, 1251-1259.
PDB code: 1jjk
11828434 K.N.Houk, J.K.Lee, D.J.Tantillo, S.Bahmanyar, and B.N.Hietbrink (2001).
Crystal structures of orotidine monophosphate decarboxylase: does the structure reveal the mechanism of nature's most proficient enzyme?
  Chembiochem, 2, 113-118.  
10889016 B.G.Miller, M.J.Snider, S.A.Short, and R.Wolfenden (2000).
Contribution of enzyme-phosphoribosyl contacts to catalysis by orotidine 5'-phosphate decarboxylase.
  Biochemistry, 39, 8113-8118.  
  11178260 J.A.Gerlt, and P.C.Babbitt (2000).
Can sequence determine function?
  Genome Biol, 1, REVIEWS0005.  
11114509 T.P.Begley, T.C.Appleby, and S.E.Ealick (2000).
The structural basis for the remarkable catalytic proficiency of orotidine 5'-monophosphate decarboxylase.
  Curr Opin Struct Biol, 10, 711-718.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.