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PDBsum entry 2j63

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protein links
Lyase PDB id
2j63
Jmol
Contents
Protein chains
333 a.a. *
Waters ×135
* Residue conservation analysis
PDB id:
2j63
Name: Lyase
Title: Crystal structure of ap endonuclease lmap from leishmania major
Structure: Ap-endonuclease. Chain: a, b. Synonym: apurinic/apyrimidinic endonuclease-redox protein, engineered: yes
Source: Leishmania major. Organism_taxid: 5664. Strain: 252. Expressed in: escherichia coli. Expression_system_taxid: 469008. Other_details: isolated in iran and provided by s. Meshnik
Resolution:
2.48Å     R-factor:   0.203     R-free:   0.246
Authors: A.E.Vidal,M.Harkiolaki,C.Gallego,V.M.Castillo-Acosta,L.M.Rui K.S.Wilson,D.Gonzalez-Pacanowska
Key ref:
A.E.Vidal et al. (2007). Crystal structure and DNA repair activities of the AP endonuclease from Leishmania major. J Mol Biol, 373, 827-838. PubMed id: 17870086 DOI: 10.1016/j.jmb.2007.08.001
Date:
25-Sep-06     Release date:   28-Aug-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
O15922  (O15922_LEIMA) -  AP-Endonuclease
Seq:
Struc:
447 a.a.
333 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.2.99.18  - DNA-(apurinic or apyrimidinic site) lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   1 term 
  Biological process     nucleic acid phosphodiester bond hydrolysis   3 terms 
  Biochemical function     lyase activity     5 terms  

 

 
DOI no: 10.1016/j.jmb.2007.08.001 J Mol Biol 373:827-838 (2007)
PubMed id: 17870086  
 
 
Crystal structure and DNA repair activities of the AP endonuclease from Leishmania major.
A.E.Vidal, M.Harkiolaki, C.Gallego, V.M.Castillo-Acosta, L.M.Ruiz-Pérez, K.Wilson, D.González-Pacanowska.
 
  ABSTRACT  
 
Apurinic/apyrimidinic endonucleases initiate the repair of abasic sites produced either spontaneously, from attack of bases by reactive oxygen species or as intermediates during base excision repair. The catalytic properties and crystal structure of Leishmania major apurinic/apyrimidinic endonuclease are described and compared with those of human APE1 and bacterial exonuclease III. The purified enzyme is shown to possess apurinic/apyrimidinic endonuclease activity of the same order as eukaryotic and prokaryotic counterparts and an equally robust 3'-phosphodiesterase activity. Consistent with this, expression of the L. major endonuclease confers resistance to both methyl methane sulphonate and H2O2 in Escherichia coli repair-deficient mutants while expression of the human homologue only reverts methyl methane sulphonate sensitivity. Structural analyses and modelling of the enzyme-DNA complex demonstrates a high degree of conservation to previously characterized homologues, although subtle differences in the active site geometry might account for the high 3'-phosphodiesterase activity. Our results confirm that the L. major's enzyme is a key element in mediating repair of apurinic/apyrimidinic sites and 3'-blocked termini and therefore must play an important role in the survival of kinetoplastid parasites after exposure to the highly oxidative environment within the host macrophage.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. The active site features and substrate modelling. (a) Electrostatic potential surface representation of the native LMAP (b) in complex with AP–DNA as modelled through superposition of the human APE1 complex (1DE8.pdb) onto the present LMAP structure. (c) Ribbon representation of LMAP with AP–DNA modelled with relevant secondary features labelled.
Figure 7.
Figure 7. Superposition of the active sites of LMAP and APE1. Divergent stereo view of selected residues of the active site of LMAP (in orange) and APE1 (in grey) superposed. Part of the AP site-containing DNA strand from 1DE8.pdb is represented semi-transparent.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 373, 827-838) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21353648 D.O.Onyango, A.Naguleswaran, S.Delaplane, A.Reed, M.R.Kelley, M.M.Georgiadis, and W.J.Sullivan (2011).
Base excision repair apurinic/apyrimidinic endonucleases in apicomplexan parasite Toxoplasma gondii.
  DNA Repair (Amst), 10, 466-475.  
20974932 B.Baños, L.Villar, M.Salas, and M.de Vega (2010).
Intrinsic apurinic/apyrimidinic (AP) endonuclease activity enables Bacillus subtilis DNA polymerase X to recognize, incise, and further repair abasic sites.
  Proc Natl Acad Sci U S A, 107, 19219-19224.  
  20976268 D.G.Passos-Silva, M.A.Rajão, P.H.Nascimento de Aguiar, J.P.Vieira-da-Rocha, C.R.Machado, and C.Furtado (2010).
Overview of DNA Repair in Trypanosoma cruzi, Trypanosoma brucei, and Leishmania major.
  J Nucleic Acids, 2010, 840768.  
19181704 V.M.Castillo-Acosta, L.M.Ruiz-Pérez, W.Yang, D.González-Pacanowska, and A.E.Vidal (2009).
Identification of a residue critical for the excision of 3'-blocking ends in apurinic/apyrimidinic endonucleases of the Xth family.
  Nucleic Acids Res, 37, 1829-1842.  
18656547 V.M.Castillo-Acosta, A.M.Estévez, A.E.Vidal, L.M.Ruiz-Perez, and D.González-Pacanowska (2008).
Depletion of dimeric all-alpha dUTPase induces DNA strand breaks and impairs cell cycle progression in Trypanosoma brucei.
  Int J Biochem Cell Biol, 40, 2901-2913.  
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.