PDBsum entry 2aa3

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Oxidoreductase PDB id
Protein chains
316 a.a. *
SO4 ×2
AP0 ×4
Waters ×479
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of plasmodium vivax lactate dehydrogenase complex with apadh
Structure: L-lactate dehydrogenase. Chain: a, b, c, d. Engineered: yes
Source: Plasmodium vivax. Malaria parasite p. Vivax. Organism_taxid: 5855. Gene: ldh. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
2.05Å     R-factor:   0.192     R-free:   0.226
Authors: A.Chaikuad,V.Fairweather,R.Conners,T.Joseph-Horne,D.Turgut- Balik,R.L.Brady
Key ref:
A.Chaikuad et al. (2005). Structure of lactate dehydrogenase from Plasmodium vivax: complexes with NADH and APADH. Biochemistry, 44, 16221-16228. PubMed id: 16331982 DOI: 10.1021/bi051416y
13-Jul-05     Release date:   10-Jan-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q4PRK9  (Q4PRK9_PLAVI) -  L-lactate dehydrogenase
316 a.a.
316 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - L-lactate dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (S)-lactate + NAD+ = pyruvate + NADH
Bound ligand (Het Group name = AP0)
matches with 95.00% similarity
= pyruvate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   3 terms 
  Biochemical function     catalytic activity     5 terms  


DOI no: 10.1021/bi051416y Biochemistry 44:16221-16228 (2005)
PubMed id: 16331982  
Structure of lactate dehydrogenase from Plasmodium vivax: complexes with NADH and APADH.
A.Chaikuad, V.Fairweather, R.Conners, T.Joseph-Horne, D.Turgut-Balik, R.L.Brady.
Malaria caused by Plasmodium vivax is a major cause of global morbidity and, in rare cases, mortality. Lactate dehydrogenase is an essential Plasmodium protein and, therefore, a potential antimalarial drug target. Ideally, drugs directed against this target would be effective against both major species of Plasmodium, P. falciparum and P. vivax. In this study, the crystal structure of the lactate dehydrogenase protein from P. vivax has been solved and is compared to the equivalent structure from the P. falciparum enzyme. The active sites and cofactor binding pockets of both enzymes are found to be highly similar and differentiate these enzymes from their human counterparts. These structures suggest effective inhibition of both enzymes should be readily achievable with a common inhibitor. The crystal structures of both enzymes have also been solved in complex with the synthetic cofactor APADH. The unusual cofactor binding site in these Plasmodium enzymes is found to readily accommodate both NADH and APADH, explaining why the Plasmodium enzymes retain enzymatic activity in the presence of this synthetic cofactor.

Literature references that cite this PDB file's key reference

  PubMed id Reference
17875391 P.Gayathri, H.Balaram, and M.R.Murthy (2007).
Structural biology of plasmodial proteins.
  Curr Opin Struct Biol, 17, 744-754.  
17461976 V.Wiwanitkit (2007).
Plasmodium and host lactate dehydrogenase molecular function and biological pathways: implication for antimalarial drug discovery.
  Chem Biol Drug Des, 69, 280-283.  
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