PDBsum entry 1pzf

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Oxidoreductase PDB id
Protein chains
328 a.a. *
OXL ×4
A3D ×4
Waters ×374
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: T.Gondii ldh1 ternary complex with apad+ and oxalate
Structure: Lactate dehydrogenase. Chain: a, b, c, d. Synonym: ldh. Engineered: yes
Source: Toxoplasma gondii. Organism_taxid: 5811. Gene: lactate dehydrogenase. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
2.20Å     R-factor:   0.177     R-free:   0.218
Authors: K.L.Kavanagh,R.A.Elling,D.K.Wilson
Key ref:
K.L.Kavanagh et al. (2004). Structure of Toxoplasma gondii LDH1: active-site differences from human lactate dehydrogenases and the structural basis for efficient APAD+ use. Biochemistry, 43, 879-889. PubMed id: 14744130 DOI: 10.1021/bi035108g
10-Jul-03     Release date:   24-Feb-04    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P90613  (P90613_TOXGO) -  Lactate dehydrogenase
329 a.a.
328 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 = OXL)
matches with 71.00% similarity
Bound ligand (Het Group name = A3D)
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   4 terms 
  Biochemical function     catalytic activity     6 terms  


DOI no: 10.1021/bi035108g Biochemistry 43:879-889 (2004)
PubMed id: 14744130  
Structure of Toxoplasma gondii LDH1: active-site differences from human lactate dehydrogenases and the structural basis for efficient APAD+ use.
K.L.Kavanagh, R.A.Elling, D.K.Wilson.
While within a human host the opportunistic pathogen Toxoplasma gondii relies heavily on glycolysis for its energy needs. Lactate dehydrogenase (LDH), the terminal enzyme in anaerobic glycolysis necessary for NAD(+) regeneration, therefore represents an attractive therapeutic target. The tachyzoite stage lactate dehydrogenase (LDH1) from the parasite T. gondii has been crystallized in apo form and in ternary complexes containing NAD(+) or the NAD(+)-analogue 3-acetylpyridine adenine dinucleotide (APAD(+)) and sulfate or the inhibitor oxalate. Comparison of the apo and ternary models shows an active-site loop that becomes ordered upon substrate binding. This active-site loop is five residues longer than in most LDHs and necessarily adopts a different conformation. While loop isomerization is fully rate-limiting in prototypical LDHs, kinetic data suggest that LDH1's rate is limited by chemical steps. The importance of charge neutralization in ligand binding is supported by the complexes that have been crystallized as well as fluorescence quenching experiments performed with ligands at low and high pH. A methionine that replaces a serine residue and displaces an ordered water molecule often seen in LDH structures provides a structural explanation for reduced substrate inhibition. Superimposition of LDH1 with human muscle- and heart-specific LDH isoforms reveals differences in residues that line the active site that increase LDH1's hydrophobicity. These differences will aid in designing inhibitors specific for LDH1 that may be useful in treating toxoplasmic encephalitis and other complications that arise in immune-compromised individuals.

Literature references that cite this PDB file's key reference

  PubMed id Reference
17459101 D.K.Shoemark, M.J.Cliff, R.B.Sessions, and A.R.Clarke (2007).
Enzymatic properties of the lactate dehydrogenase enzyme from Plasmodium falciparum.
  FEBS J, 274, 2738-2748.  
15932938 Q.Yang, X.Wang, L.Ye, M.Mentrikoski, E.Mohammadi, Y.M.Kim, and P.C.Maloney (2005).
Experimental tests of a homology model for OxlT, the oxalate transporter of Oxalobacter formigenes.
  Proc Natl Acad Sci U S A, 102, 8513-8518.
PDB code: 1zc7
15317584 A.K.Tripathi, P.V.Desai, A.Pradhan, S.I.Khan, M.A.Avery, L.A.Walker, and B.L.Tekwani (2004).
An alpha-proteobacterial type malate dehydrogenase may complement LDH function in Plasmodium falciparum. Cloning and biochemical characterization of the enzyme.
  Eur J Biochem, 271, 3488-3502.  
15459194 F.Al-Anouti, S.Tomavo, S.Parmley, and S.Ananvoranich (2004).
The expression of lactate dehydrogenase is important for the cell cycle of Toxoplasma gondii.
  J Biol Chem, 279, 52300-52311.  
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