4ND3: Crystal Structure Of The Lactate Dehydrogenase From Cryptosporidium Parvum Complexed With Substrate (l-lactic Acid) And Cofactor (b- Nicotinamide Adenine Dinucleotide)

Citation:
Abstract
The protozoan parasite Cryptosporidium parvum causes waterborne diseases worldwide. There is no effective therapy for C. parvum infection. The parasite depends mainly on glycolysis for energy production. Lactate dehydrogenase is a major regulator of glycolysis. This paper describes the biochemical characterization of C. parvum lactate dehydrogenase and high resolution crystal structures of the apo-enzyme and four ternary complexes. The ternary complexes capture the enzyme bound to NAD/NADH or its 3-acetylpyridine analog in the cofactor binding pocket, while the substrate binding site is occupied by one of the following ligands: lactate, pyruvate or oxamate. The results reveal distinctive features of the parasitic enzyme. For example, C. parvum lactate dehydrogenase prefers the acetylpyridine analog of NADH as a cofactor. Moreover, it is slightly less sensitive to gossypol inhibition compared with mammalian lactate dehydrogenases and not inhibited by excess pyruvate. The active site loop and the antigenic loop in C. parvum lactate dehydrogenase are considerably different from those in the human counterpart. Structural features and enzymatic properties of C. parvum lactate dehydrogenase are similar to enzymes from related parasites. Structural comparison with malate dehydrogenase supports a common ancestry for the two genes.
PDB ID: 4ND3Download
MMDB ID: 125583
PDB Deposition Date: 2013/10/25
Updated in MMDB: 2014/12
Experimental Method:
x-ray diffraction
Resolution: 2.05  Å
Source Organism:
Similar Structures:
Biological Unit for 4ND3: tetrameric; determined by author and by software (PISA)
Molecular Components in 4ND3
Label Count Molecule
Proteins (4 molecules)
4
Lactate Dehydrogenase, Adjacent Gene Encodes Predicted Malate Dehydrogenase
Molecule annotation
Chemicals (12 molecules)
1
4
2
2
3
6
* Click molecule labels to explore molecular sequence information.

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