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PDBsum entry 1hkv
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Lyase PDB id
1hkv

 

 

 

 

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Contents
Protein chains
446 a.a. *
Ligands
LYS ×2
PLP ×2
Waters ×236
* Residue conservation analysis
PDB id:
1hkv
Name: Lyase
Title: Mycobacterium diaminopimelate dicarboxylase (lysa)
Structure: Diaminopimelate decarboxylase. Chain: a, b. Synonym: dap decarboxylase, meso-diaminopimelate decarboxylase, lysa. Engineered: yes. Other_details: complexed with cofactor plp and product lysine
Source: Mycobacterium tuberculosis. Organism_taxid: 83332. Strain: h37rv. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: c-term 6-his tag
Biol. unit: Dimer (from PDB file)
Resolution:
2.60Å     R-factor:   0.227     R-free:   0.268
Authors: K.Gokulan,B.Rupp,M.S.Pavelka Jr,W.R.Jacobs Jr,J.C.Sacchettini,Tb Structural Genomics Consortium (Tbsgc)
Key ref:
K.Gokulan et al. (2003). Crystal structure of Mycobacterium tuberculosis diaminopimelate decarboxylase, an essential enzyme in bacterial lysine biosynthesis. J Biol Chem, 278, 18588-18596. PubMed id: 12637582 DOI: 10.1074/jbc.M301549200
Date:
11-Mar-03     Release date:   20-Mar-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P9WIU7  (DCDA_MYCTU) -  Diaminopimelate decarboxylase from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Seq:
Struc: 		447 a.a.
446 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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-diaminopimelate + H+ = L-lysine + CO2
meso-2,6-diaminopimelate
 + H(+)
 = L-lysine
 +
CO2
Bound ligand (Het Group name = LYS)
corresponds exactly
      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

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M301549200 J Biol Chem 278:18588-18596 (2003)
PubMed id: 12637582  
 
 
Crystal structure of Mycobacterium tuberculosis diaminopimelate decarboxylase, an essential enzyme in bacterial lysine biosynthesis.
K.Gokulan, B.Rupp, M.S.Pavelka, W.R.Jacobs, J.C.Sacchettini.
 
  ABSTRACT  
 
The Mycobacterium tuberculosis lysA gene encodes the enzyme meso-diaminopimelate decarboxylase (DAPDC), a pyridoxal-5'-phosphate (PLP)-dependent enzyme. The enzyme catalyzes the final step in the lysine biosynthetic pathway converting meso-diaminopimelic acid (DAP) to l-lysine. The lysA gene of M. tuberculosis H37Rv has been established as essential for bacterial survival in immunocompromised mice, demonstrating that de novo biosynthesis of lysine is essential for in vivo viability. Drugs targeted against DAPDC could be efficient anti-tuberculosis drugs, and the three-dimensional structure of DAPDC from M. tuberculosis complexed with reaction product lysine and the ternary complex with PLP and lysine in the active site has been determined. The first structure of a DAPDC confirms its classification as a fold type III PLP-dependent enzyme. The structure shows a stable 2-fold dimer in head-to-tail arrangement of a triose-phosphate isomerase (TIM) barrel-like alpha/beta domain and a C-terminal beta sheet domain, similar to the ornithine decarboxylase (ODC) fold family. PLP is covalently bound via an internal aldimine, and residues from both domains and both subunits contribute to the binding pocket. Comparison of the structure with eukaryotic ODCs, in particular with a di-fluoromethyl ornithine (DMFO)-bound ODC from Trypanosoma bruceii, indicates that corresponding DAP-analogues might be potential inhibitors for mycobacterial DAPDCs.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. Multiple sequence alignment of PLP-dependent enzymes. Top line indicates regions of partially conserved or important binding motives or residues. Alignment carried out with ClustalW 1.8.2 (40). Color key: green, polar residues; red, hydrophobic residues; blue, negatively charged; and magenta, positively charged. 		Figure 6.
Fig. 6. Schematic representation of ligand binding interactions in active site pocket of DAPDC. Residues of both homodimer subunits contribute to PLP and to lysine binding. This figure was created by LIGPLOT (43).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 18588-18596) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21190106 H.Muramatsu, Y.Suzuki, T.Imai, S.Ueshima, J.Ozaki, Y.Matsui, S.Kato, K.Ohnishi, N.Kimoto, H.Yamamoto, and S.Nagata (2011).
Discovery and characterization of D: -phenylserine deaminase from Arthrobacter sp. TKS1.
  Appl Microbiol Biotechnol, 90, 159-172.  
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
19099550 K.Raman, Y.Kalidas, and N.Chandra (2008).
targetTB: A target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis.
  BMC Syst Biol, 2, 109.  
17579770 C.A.Hutton, M.A.Perugini, and J.A.Gerrard (2007).
Inhibition of lysine biosynthesis: an evolving antibiotic strategy.
  Mol Biosyst, 3, 458-465.  
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
16557306 D.Alexeev, R.L.Baxter, D.J.Campopiano, O.Kerbarh, L.Sawyer, N.Tomczyk, R.Watt, and S.P.Webster (2006).
Suicide inhibition of alpha-oxamine synthases: structures of the covalent adducts of 8-amino-7-oxononanoate synthase with trifluoroalanine.
  Org Biomol Chem, 4, 1209-1212.
PDB code: 2g6w
16525757 R.A.Azevedo, M.Lancien, and P.J.Lea (2006).
The aspartic acid metabolic pathway, an exciting and essential pathway in plants.
  Amino Acids, 30, 143-162.  
16789813 S.Hasan, S.Daugelat, P.S.Rao, and M.Schreiber (2006).
Prioritizing genomic drug targets in pathogens: application to Mycobacterium tuberculosis.
  PLoS Comput Biol, 2, e61.  
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.  
16478688 V.L.Arcus, J.S.Lott, J.M.Johnston, and E.N.Baker (2006).
The potential impact of structural genomics on tuberculosis drug discovery.
  Drug Discov Today, 11, 28-34.  
  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.  
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.  
15329673 P.R.Hall, R.Zheng, L.Antony, M.Pusztai-Carey, P.R.Carey, and V.C.Yee (2004).
Transcarboxylase 5S structures: assembly and catalytic mechanism of a multienzyme complex subunit.
  EMBO J, 23, 3621-3631.
PDB codes: 1rqb 1rqe 1rqh 1rr2 1s3h 1u5j
14675542 C.V.Smith, and J.C.Sacchettini (2003).
Mycobacterium tuberculosis: a model system for structural genomics.
  Curr Opin Struct Biol, 13, 658-664.  
12915092 M.Bellinzoni, and G.Riccardi (2003).
Techniques and applications: The heterologous expression of Mycobacterium tuberculosis genes is an uphill road.
  Trends Microbiol, 11, 351-358.  
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.  
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.

 

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