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Biochemical and structural characterization of Cryptosporidium parvum Lactate dehydrogenase.

Cook WJ, Senkovich O, Hernandez A, Speed H, Chattopadhyay D
Int J Biol Macromol 74 608-19 (2015)
Related entries: 4nd1, 4nd2, 4nd3, 4nd4

Cited: 11 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)


Articles citing this publication (10)

  1. Metabolic Signatures of Cryptosporidiumparvum-Infected HCT-8 Cells and Impact of Selected Metabolic Inhibitors on C. parvum Infection under Physioxia and Hyperoxia. Vélez J, Velasquez Z, Silva LMR, Gärtner U, Failing K, Daugschies A, Mazurek S, Hermosilla C, Taubert A. Biology (Basel) 10 60 (2021)
  2. Novel lactate dehydrogenase inhibitors with in vivo efficacy against Cryptosporidium parvum. Li K, Nader SM, Zhang X, Ray BC, Kim CY, Das A, Witola WH. PLoS Pathog 15 e1007953 (2019)
  3. Structurally Linked Dynamics in Lactate Dehydrogenases of Evolutionarily Distinct Species. Varga MJ, Dzierlenga MW, Schwartz SD. Biochemistry 56 2488-2496 (2017)
  4. A mechanistic kinetic description of lactate dehydrogenase elucidating cancer diagnosis and inhibitor evaluation. Tang P, Xu J, Oliveira CL, Li ZJ, Liu S. J Enzyme Inhib Med Chem 32 564-571 (2017)
  5. Molecular cloing and bioinformatics analysis of lactate dehydrogenase from Taenia multiceps. Guo C, Wang Y, Huang X, Wang N, Yan M, He R, Gu X, Xie Y, Lai W, Jing B, Peng X, Yang G. Parasitol Res 116 2845-2852 (2017)
  6. Biological characterization of D-lactate dehydrogenase responsible for high-yield production of D-phenyllactic acid in Sporolactobacillus inulinus. Cheng YY, Park TH, Seong H, Kim TJ, Han NS. Microb Biotechnol 15 2717-2729 (2022)
  7. Polyphenolic Profile of Herniaria hemistemon Aerial Parts Extract and Assessment of Its Anti-Cryptosporidiosis in a Murine Model: In Silico Supported In Vivo Study. Ghareeb MA, Sobeh M, Aboushousha T, Esmat M, Mohammed HS, El-Wakil ES. Pharmaceutics 15 415 (2023)
  8. Relative catalytic efficiencies and transcript levels of three d- and two l-lactate dehydrogenases for optically pure d-lactate production in Sporolactobacillus inulinus. Wu B, Yu Q, Zheng S, Pedroso MM, Guddat LW, He B, Schenk G. Microbiologyopen 8 e00704 (2019)
  9. Annona muricata Leaf as an Anti-Cryptosporidial Agent: An In Silico Molecular Docking Analysis and In Vivo Studies. El-Wakil ES, Abdelmaksoud HF, Wakid MH, Alsulami MN, Hammam O, Albohiri HH, Ghallab MMI. Pharmaceuticals (Basel) 16 878 (2023)
  10. Combination of inhibitors for two glycolytic enzymes portrays high synergistic efficacy against Cryptosporidium parvum. Khan SM, Bajwa MR, Lahar RY, Witola WH. Antimicrob Agents Chemother 67 e0056923 (2023)


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