4nd5 Citations

Biochemical and structural characterization of Cryptosporidium parvum Lactate dehydrogenase.

Int J Biol Macromol 74 608-19 (2015)
Related entries: 4nd1, 4nd2, 4nd3, 4nd4

Cited: 15 times
EuropePMC logo PMID: 25542170

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.

Articles - 4nd5 mentioned but not cited (1)

  1. Phasertng: directed acyclic graphs for crystallographic phasing. McCoy AJ, Stockwell DH, Sammito MD, Oeffner RD, Hatti KS, Croll TI, Read RJ. Acta Crystallogr D Struct Biol 77 1-10 (2021)


Reviews citing this publication (2)

  1. Malate dehydrogenase in parasitic protozoans: roles in metabolism and potential therapeutic applications. Springer AL, Agrawal S, Chang EP. Essays Biochem 68 235-251 (2024)
  2. Treating cryptosporidiosis: A review on drug discovery strategies. Lenière AC, Vlandas A, Follet J. Int J Parasitol Drugs Drug Resist 25 100542 (2024)

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