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PDBsum entry 7odc

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Lyase PDB id
7odc
Jmol
Contents
Protein chain
387 a.a. *
Ligands
PLP
Waters ×421
* Residue conservation analysis
PDB id:
7odc
Name: Lyase
Title: Crystal structure ornithine decarboxylase from mouse, trunca residues from thE C-terminus, to 1.6 angstrom resolution
Structure: Protein (ornithine decarboxylase). Chain: a. Synonym: odc, modc, modc'. Engineered: yes. Mutation: yes. Other_details: schiff-base linkage between plp and k69
Source: Mus musculus. House mouse. Organism_taxid: 10090. Cell_line: s49.1. Tissue: lymphoma. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: the gene was cloned from a balb-c mouse lymp line in which the odc gene was amplified by selection with
Biol. unit: Dimer (from PDB file)
Resolution:
1.60Å     R-factor:   0.199     R-free:   0.232
Authors: A.D.Kern,M.A.Oliveira,P.Coffino,M.L.Hackert
Key ref:
A.D.Kern et al. (1999). Structure of mammalian ornithine decarboxylase at 1.6 A resolution: stereochemical implications of PLP-dependent amino acid decarboxylases. Structure, 7, 567-581. PubMed id: 10378276 DOI: 10.1016/S0969-2126(99)80073-2
Date:
03-Mar-99     Release date:   22-Oct-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00860  (DCOR_MOUSE) -  Ornithine decarboxylase
Seq:
Struc:
461 a.a.
387 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.4.1.1.17  - Ornithine decarboxylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Spermine Biosynthesis
      Reaction: L-ornithine = putrescine + CO2
L-ornithine
= putrescine
+ CO(2)
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Bound ligand (Het Group name = PLP) matches with 93.75% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   3 terms 
  Biological process     response to virus   8 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(99)80073-2 Structure 7:567-581 (1999)
PubMed id: 10378276  
 
 
Structure of mammalian ornithine decarboxylase at 1.6 A resolution: stereochemical implications of PLP-dependent amino acid decarboxylases.
A.D.Kern, M.A.Oliveira, P.Coffino, M.L.Hackert.
 
  ABSTRACT  
 
BACKGROUND: Pyridoxal-5'-phosphate (PLP) dependent enzymes catalyze a broad range of reactions, resulting in bond cleavage at C alpha, C beta, or C gamma carbons of D and L amino acid substrates. Ornithine decarboxylase (ODC) is a PLP-dependent enzyme that controls a critical step in the biosynthesis of polyamines, small organic polycations whose controlled levels are essential for proper growth. ODC inhibition has applications for the treatment of certain cancers and parasitic ailments such as African sleeping sickness. RESULTS: The structure of truncated mouse ODC (mODC') was determined by multiple isomorphous replacement methods and refined to 1.6 A resolution. This is the first structure of a Group IV decarboxylase. The monomer contains two domains: an alpha/beta barrel that binds the cofactor, and a second domain consisting mostly of beta structure. Only the dimer is catalytically active, as the active sites are constructed of residues from both monomers. The interactions stabilizing the dimer shed light on its regulation by antizyme. The overall structure and the environment of the cofactor are compared with those of alanine racemase. CONCLUSIONS: The analysis of the mODC' structure and its comparison with alanine racemase, together with modeling studies of the external aldimine intermediate, provide insight into the stereochemical characteristics of PLP-dependent decarboxylation. The structure comparison reveals stereochemical differences with other PLP-dependent enzymes and the bacterial ODC. These characteristics may be exploited in the design of new inhibitors specific for eukaryotic and bacterial ODCs, and provide the basis for a detailed understanding of the mechanism by which these enzymes regulate reaction specificity.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. Active site of mODC′ and comparison with ALR. (a) Schematic drawing of the mODC′ active site illustrating the hydrogen-bond interactions. Residues shown in bold face are nearer the viewer. (b) Stereo figure of the active site of mODC′ with electron density superimposed with its model. K69 of mODC′ is in Schiff-base linkage to the cofactor, E274 pairs with the pyridine ring nitrogen N1, and H197 stacks on the si face of the cofactor ring. Note the angle between K69 and the pyridine ring of the cofactor exposing the si face. The map is a 2F[o]–F[c] map at 1.6 Å resolution contoured at 1.2σ. (c) A view of the ALR and mODC′ active sites resulting from the superposition of their cofactor rings. The mODC′ active site is depicted in light gray. The figures were generated using BOBSCRIPT [83], MOLSCRIPT [80] and Raster3D [81].
 
  The above figure is reprinted by permission from Cell Press: Structure (1999, 7, 567-581) copyright 1999.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20512387 G.Colotti, and A.Ilari (2011).
Polyamine metabolism in Leishmania: from arginine to trypanothione.
  Amino Acids, 40, 269-285.  
20217058 I.P.Ivanov, A.E.Firth, and J.F.Atkins (2010).
Recurrent emergence of catalytically inactive ornithine decarboxylase homologous forms that likely have regulatory function.
  J Mol Evol, 70, 289-302.  
19166624 G.Steinkellner, R.Rader, G.G.Thallinger, C.Kratky, and K.Gruber (2009).
VASCo: computation and visualization of annotated protein surface contacts.
  BMC Bioinformatics, 10, 32.  
19635796 K.L.Su, Y.F.Liao, H.C.Hung, and G.Y.Liu (2009).
Critical factors determining dimerization of human antizyme inhibitor.
  J Biol Chem, 284, 26768-26777.  
19543810 S.Weyand, G.Kefala, D.I.Svergun, and M.S.Weiss (2009).
The three-dimensional structure of diaminopimelate decarboxylase from Mycobacterium tuberculosis reveals a tetrameric enzyme organisation.
  J Struct Funct Genomics, 10, 209-217.
PDB code: 2o0t
18310073 A.A.Moya-García, J.Ruiz-Pernía, S.Martí, F.Sánchez-Jiménez, and I.Tuñón (2008).
Analysis of the decarboxylation step in mammalian histidine decarboxylase. A computational study.
  J Biol Chem, 283, 12393-12401.  
18235846 A.Jhingran, P.K.Padmanabhan, S.Singh, K.Anamika, A.A.Bakre, S.Bhattacharya, A.Bhattacharya, N.Srinivasan, and R.Madhubala (2008).
Characterization of the Entamoeba histolytica Ornithine Decarboxylase-Like Enzyme.
  PLoS Negl Trop Dis, 2, e115.  
18558098 I.Jariel-Encontre, G.Bossis, and M.Piechaczyk (2008).
Ubiquitin-independent degradation of proteins by the proteasome.
  Biochim Biophys Acta, 1786, 153-177.  
18369191 S.Albeck, O.Dym, T.Unger, Z.Snapir, Z.Bercovich, and C.Kahana (2008).
Crystallographic and biochemical studies revealing the structural basis for antizyme inhibitor function.
  Protein Sci, 17, 793-802.
PDB code: 3btn
18508763 T.Hu, D.Wu, J.Chen, J.Ding, H.Jiang, and X.Shen (2008).
The catalytic intermediate stabilized by a "down" active site loop for diaminopimelate decarboxylase from Helicobacter pylori. Enzymatic characterization with crystal structure analysis.
  J Biol Chem, 283, 21284-21293.  
17626020 J.Lee, A.J.Michael, D.Martynowski, E.J.Goldsmith, and M.A.Phillips (2007).
Phylogenetic diversity and the structural basis of substrate specificity in the beta/alpha-barrel fold basic amino acid decarboxylases.
  J Biol Chem, 282, 27115-27125.
PDB codes: 2plj 2plk
17305368 R.Shah, R.Akella, E.J.Goldsmith, and M.A.Phillips (2007).
X-ray structure of Paramecium bursaria Chlorella virus arginine decarboxylase: insight into the structural basis for substrate specificity.
  Biochemistry, 46, 2831-2841.
PDB codes: 2nv9 2nva
16601692 M.A.Hoyt, J.Zich, J.Takeuchi, M.Zhang, C.Govaerts, and P.Coffino (2006).
Glycine-alanine repeats impair proper substrate unfolding by the proteasome.
  EMBO J, 25, 1720-1729.  
16354653 Y.Yamaguchi, Y.Takatsuka, S.Matsufuji, Y.Murakami, and Y.Kamio (2006).
Characterization of a counterpart to Mammalian ornithine decarboxylase antizyme in prokaryotes.
  J Biol Chem, 281, 3995-4001.  
15735332 D.I.Dutyshev, E.L.Darii, N.P.Fomenkova, I.V.Pechik, K.M.Polyakov, S.V.Nikonov, N.S.Andreeva, and B.S.Sukhareva (2005).
Structure of Escherichia coli glutamate decarboxylase (GADalpha) in complex with glutarate at 2.05 angstroms resolution.
  Acta Crystallogr D Biol Crystallogr, 61, 230-235.
PDB code: 1xey
15189147 A.C.Eliot, and J.F.Kirsch (2004).
Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations.
  Annu Rev Biochem, 73, 383-415.  
15583399 C.N.Patel, R.S.Adcock, K.G.Sell, and M.A.Oliveira (2004).
Crystallization, X-ray diffraction and oligomeric characterization of arginine decarboxylase from Yersinia pestis, a key polyamine biosynthetic enzyme.
  Acta Crystallogr D Biol Crystallogr, 60, 2396-2398.  
15791490 J.H.Lee, M.Y.Son, M.Y.Yoon, J.D.Choi, and Y.T.Kim (2004).
Isolation and characterization of ornithine decarboxylase gene from flounder (Paralichthys olivaceus).
  Mar Biotechnol (NY), 6, 453-462.  
14688254 M.Zhang, and P.Coffino (2004).
Repeat sequence of Epstein-Barr virus-encoded nuclear antigen 1 protein interrupts proteasome substrate processing.
  J Biol Chem, 279, 8635-8641.  
15190062 R.Shah, C.S.Coleman, K.Mir, J.Baldwin, J.L.Van Etten, N.V.Grishin, A.E.Pegg, B.A.Stanley, and M.A.Phillips (2004).
Paramecium bursaria chlorella virus-1 encodes an unusual arginine decarboxylase that is a close homolog of eukaryotic ornithine decarboxylases.
  J Biol Chem, 279, 35760-35767.  
14745158 Y.Takatsuka, and Y.Kamio (2004).
Molecular dissection of the Selenomonas ruminantium cell envelope and lysine decarboxylase involved in the biosynthesis of a polyamine covalently linked to the cell wall peptidoglycan layer.
  Biosci Biotechnol Biochem, 68, 1.  
12952559 B.E.Shakhnovich, J.M.Harvey, S.Comeau, D.Lorenz, C.DeLisi, and E.Shakhnovich (2003).
ELISA: structure-function inferences based on statistically significant and evolutionarily inspired observations.
  BMC Bioinformatics, 4, 34.  
14675542 C.V.Smith, and J.C.Sacchettini (2003).
Mycobacterium tuberculosis: a model system for structural genomics.
  Curr Opin Struct Biol, 13, 658-664.  
12637582 K.Gokulan, B.Rupp, M.S.Pavelka, W.R.Jacobs, and J.C.Sacchettini (2003).
Crystal structure of Mycobacterium tuberculosis diaminopimelate decarboxylase, an essential enzyme in bacterial lysine biosynthesis.
  J Biol Chem, 278, 18588-18596.
PDB codes: 1hkv 1hkw
12557188 L.Birkholtz, F.Joubert, A.W.Neitz, and A.I.Louw (2003).
Comparative properties of a three-dimensional model of Plasmodium falciparum ornithine decarboxylase.
  Proteins, 50, 464-473.
PDB code: 1m9v
12672797 L.K.Jackson, E.J.Goldsmith, and M.A.Phillips (2003).
X-ray structure determination of Trypanosoma brucei ornithine decarboxylase bound to D-ornithine and to G418: insights into substrate binding and ODC conformational flexibility.
  J Biol Chem, 278, 22037-22043.
PDB code: 1njj
12660156 M.Zhang, C.M.Pickart, and P.Coffino (2003).
Determinants of proteasome recognition of ornithine decarboxylase, a ubiquitin-independent substrate.
  EMBO J, 22, 1488-1496.  
14690429 P.B.Balbo, C.N.Patel, K.G.Sell, R.S.Adcock, S.Neelakantan, P.A.Crooks, and M.A.Oliveira (2003).
Spectrophotometric and steady-state kinetic analysis of the biosynthetic arginine decarboxylase of Yersinia pestis utilizing arginine analogues as inhibitors and alternative substrates.
  Biochemistry, 42, 15189-15196.  
12499548 S.Eswaramoorthy, S.Gerchman, V.Graziano, H.Kycia, F.W.Studier, and S.Swaminathan (2003).
Structure of a yeast hypothetical protein selected by a structural genomics approach.
  Acta Crystallogr D Biol Crystallogr, 59, 127-135.
PDB codes: 1b54 1ct5
11856852 C.Momany, V.Levdikov, L.Blagova, and K.Crews (2002).
Crystallization of diaminopimelate decarboxylase from Escherichia coli, a stereospecific D-amino-acid decarboxylase.
  Acta Crystallogr D Biol Crystallogr, 58, 549-552.  
12359729 H.Chen, A.MacDonald, and P.Coffino (2002).
Structural elements of antizymes 1 and 2 are required for proteasomal degradation of ornithine decarboxylase.
  J Biol Chem, 277, 45957-45961.  
11576438 C.Hanfrey, S.Sommer, M.J.Mayer, D.Burtin, and A.J.Michael (2001).
Arabidopsis polyamine biosynthesis: absence of ornithine decarboxylase and the mechanism of arginine decarboxylase activity.
  Plant J, 27, 551-560.  
11933245 H.Kagamiyama, and H.Hayashi (2001).
Release of enzyme strain during catalysis reduces the activation energy barrier.
  Chem Rec, 1, 385-394.  
11933250 P.Christen, and P.K.Mehta (2001).
From cofactor to enzymes. The molecular evolution of pyridoxal-5'-phosphate-dependent enzymes.
  Chem Rec, 1, 436-447.  
10673430 G.Schneider, H.Käck, and Y.Lindqvist (2000).
The manifold of vitamin B6 dependent enzymes.
  Structure, 8, R1-R6.  
10781034 P.Coffino (2000).
Polyamines in spermiogenesis: not now, darling.
  Proc Natl Acad Sci U S A, 97, 4421-4423.  
11073919 Y.Takatsuka, Y.Yamaguchi, M.Ono, and Y.Kamio (2000).
Gene cloning and molecular characterization of lysine decarboxylase from Selenomonas ruminantium delineate its evolutionary relationship to ornithine decarboxylases from eukaryotes.
  J Bacteriol, 182, 6732-6741.  
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 code is shown on the right.