Biochemical and structural characterization of Cryptosporidium parvum Lactate dehydrogenase

William J. Cook, Olga Senkovich, Agustin Hernandez, Haley Speed, Debasish Chattopadhyay

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)608-619
Number of pages12
JournalInternational Journal of Biological Macromolecules
Volume74
DOIs
StatePublished - Mar 1 2015

Fingerprint

Cryptosporidium parvum
L-Lactate Dehydrogenase
NAD
Enzymes
Parasites
Pyruvic Acid
Glycolysis
Lactate Dehydrogenases
Gossypol
Malate Dehydrogenase
Lactic Acid
Genes
Crystal structure
Binding Sites
Catalytic Domain
Ligands
Substrates
Infection

Keywords

  • Cryptosporidium parvum
  • Crystal structure
  • Lactate dehydrogenase

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Cite this

Biochemical and structural characterization of Cryptosporidium parvum Lactate dehydrogenase. / Cook, William J.; Senkovich, Olga; Hernandez, Agustin; Speed, Haley; Chattopadhyay, Debasish.

In: International Journal of Biological Macromolecules, Vol. 74, 01.03.2015, p. 608-619.

Research output: Contribution to journalArticle

Cook, William J. ; Senkovich, Olga ; Hernandez, Agustin ; Speed, Haley ; Chattopadhyay, Debasish. / Biochemical and structural characterization of Cryptosporidium parvum Lactate dehydrogenase. In: International Journal of Biological Macromolecules. 2015 ; Vol. 74. pp. 608-619.
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