4ND1

Crystal structure of the lactate dehydrogenase from cryptosporidium parvum complexed with cofactor (b-nicotinamide adenine dinucleotide) and inhibitor (oxamic acid)

Replaces:  2FNZ

Summary for 4ND1

• Entry DOI: 10.2210/pdb4nd1/pdb
• Related: 4ND2 4ND3 4ND4 4ND5
• Descriptor: Lactate dehydrogenase, adjacent gene encodes predicted malate dehydrogenase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, OXAMIC ACID, ... (5 entities in total)
• Functional Keywords: rossmann fold, dehydrogenase, nad binding, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• Biological source: Cryptosporidium parvum
• Total number of polymer chains: 2
• Total formula weight: 69643.04

Authors

Chattopadhyay, D.,Cook, W.J. (deposition date: 2013-10-25, release date: 2014-12-17, Last modification date: 2024-10-30)

Primary citation

Cook, W.J.,Senkovich, O.,Hernandez, A.,Speed, H.,Chattopadhyay, D.
Biochemical and structural characterization of Cryptosporidium parvum Lactate dehydrogenase.
Int.J.Biol.Macromol., 74C:608-619, 2014

PubMed 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.

PubMed: 25542170
DOI: 10.1016/j.ijbiomac.2014.12.019

Experimental method

X-RAY DIFFRACTION (2.15 Å)