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PDBsum entry 1tuf

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Lyase PDB id
1tuf
Jmol
Contents
Protein chains
434 a.a. *
Ligands
AZ1 ×2
Waters ×292
* Residue conservation analysis
PDB id:
1tuf
Name: Lyase
Title: Crystal structure of diaminopimelate decarboxylase from m. Jannaschi
Structure: Diaminopimelate decarboxylase. Chain: a, b. Synonym: dap decarboxylase. Engineered: yes
Source: Methanocaldococcus jannaschii. Organism_taxid: 2190. Gene: lysa, mj1097. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Tetramer (from PQS)
Resolution:
2.40Å     R-factor:   0.204     R-free:   0.253
Authors: K.Rajashankar,S.R.Ray,J.B.Bonanno,M.G.Pinho,G.He,H.De Lencastre,A.Tomasz,S.K.Burley,New York Sgx Research Center For Structural Genomics (Nysgxrc)
Key ref:
S.S.Ray et al. (2002). Cocrystal structures of diaminopimelate decarboxylase: mechanism, evolution, and inhibition of an antibiotic resistance accessory factor. Structure, 10, 1499-1508. PubMed id: 12429091 DOI: 10.1016/S0969-2126(02)00880-8
Date:
24-Jun-04     Release date:   20-Jul-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q58497  (DCDA_METJA) -  Diaminopimelate decarboxylase
Seq:
Struc:
438 a.a.
434 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.4.1.1.20  - Diaminopimelate decarboxylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Lysine biosynthesis (later stages)
      Reaction: Meso-2,6-diaminoheptanedioate = L-lysine + CO2
Meso-2,6-diaminoheptanedioate
=
L-lysine
Bound ligand (Het Group name = AZ1)
matches with 53.00% similarity
+ CO(2)
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     cellular amino acid biosynthetic process   3 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(02)00880-8 Structure 10:1499-1508 (2002)
PubMed id: 12429091  
 
 
Cocrystal structures of diaminopimelate decarboxylase: mechanism, evolution, and inhibition of an antibiotic resistance accessory factor.
S.S.Ray, J.B.Bonanno, K.R.Rajashankar, M.G.Pinho, G.He, H.De Lencastre, A.Tomasz, S.K.Burley.
 
  ABSTRACT  
 
Cocrystal structures of Methanococcus jannaschii diaminopimelate decarboxylase (DAPDC) bound to a substrate analog, azelaic acid, and its L-lysine product have been determined at 2.6 A and 2.0 A, respectively. This PLP-dependent enzyme is responsible for the final step of L-lysine biosynthesis in bacteria and plays a role in beta-lactam antibiotic resistance in Staphylococcus aureus. Substrate specificity derives from recognition of the L-chiral center of diaminopimelate and a system of ionic "molecular rulers" that dictate substrate length. A coupled-enzyme assay system permitted measurement of kinetic parameters for recombinant DAPDCs and inhibition constants (K(i)) for azelaic acid (89 microM) and other substrate analogs. Implications for rational design of broad-spectrum antimicrobial agents targeted against DAPDCs of drug-resistant strains of bacterial pathogens, such as Staphylococcus aureus, are discussed.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. L-Lysine Biosynthetic Pathways and DAPDC Inhibitors(A) Schematic representation of L-lysine biosynthesis pathways in bacteria.(B) Chemical structures and K[i] values (where appropriate) for substrate, product, and structurally similar inhibitors.
 
  The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 1499-1508) copyright 2002.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20085486 D.C.Smithson, A.A.Shelat, J.Baldwin, M.A.Phillips, and R.K.Guy (2010).
Optimization of a non-radioactive high-throughput assay for decarboxylase enzymes.
  Assay Drug Dev Technol, 8, 175-185.  
22477769 R.P.Joosten, J.Salzemann, V.Bloch, H.Stockinger, A.C.Berglund, C.Blanchet, E.Bongcam-Rudloff, C.Combet, A.L.Da Costa, G.Deleage, M.Diarena, R.Fabbretti, G.Fettahi, V.Flegel, A.Gisel, V.Kasam, T.Kervinen, E.Korpelainen, K.Mattila, M.Pagni, M.Reichstadt, V.Breton, I.J.Tickle, and G.Vriend (2009).
PDB_REDO: automated re-refinement of X-ray structure models in the PDB.
  J Appl Crystallogr, 42, 376-384.  
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.  
18650422 T.N.Giles, and D.E.Graham (2008).
Crenarchaeal arginine decarboxylase evolved from an S-adenosylmethionine decarboxylase enzyme.
  J Biol Chem, 283, 25829-25838.  
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
16882991 J.Cai, C.Han, T.Hu, J.Zhang, D.Wu, F.Wang, Y.Liu, J.Ding, K.Chen, J.Yue, X.Shen, and H.Jiang (2006).
Peptide deformylase is a potential target for anti-Helicobacter pylori drugs: reverse docking, enzymatic assay, and X-ray crystallography validation.
  Protein Sci, 15, 2071-2081.
PDB codes: 2ew5 2ew6 2ew7
17094151 M.Wenger, and J.Bernstein (2006).
Designing a cocrystal of gamma-amino butyric acid.
  Angew Chem Int Ed Engl, 45, 7966-7969.  
16362287 S.Jantaro, H.Kidron, D.Chesnel, A.Incharoensakdi, P.Mulo, T.Salminen, and P.Mäenpää (2006).
Structural modeling and environmental regulation of arginine decarboxylase in Synechocystis sp. PCC 6803.
  Arch Microbiol, 184, 397-406.  
  16511157 G.Kefala, L.J.Perry, and M.S.Weiss (2005).
Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of LysA (Rv1293) from Mycobacterium tuberculosis.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 782-784.  
14613936 A.Severin, K.Tabei, F.Tenover, M.Chung, N.Clarke, and A.Tomasz (2004).
High level oxacillin and vancomycin resistance and altered cell wall composition in Staphylococcus aureus carrying the staphylococcal mecA and the enterococcal vanA gene complex.
  J Biol Chem, 279, 3398-3407.  
14679244 M.Lemonnier, S.Santos-Sierra, C.Pardo-Abarrio, and R.Díaz-Orejas (2004).
Identification of residues of the kid toxin involved in autoregulation of the parD system.
  J Bacteriol, 186, 240-243.  
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.  
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
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.  
12808037 W.W.Lui, B.M.Collins, J.Hirst, A.Motley, C.Millar, P.Schu, D.J.Owen, and M.S.Robinson (2003).
Binding partners for the COOH-terminal appendage domains of the GGAs and gamma-adaptin.
  Mol Biol Cell, 14, 2385-2398.
PDB code: 1na8
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.