7NRZ

Crystal structure of malate dehydrogenase from Trypanosoma cruzi

Summary for 7NRZ

• Entry DOI: 10.2210/pdb7nrz/pdb
• Descriptor: Malate dehydrogenase, 1,2-ETHANEDIOL, DI(HYDROXYETHYL)ETHER, ... (7 entities in total)
• Functional Keywords: oxidoreductase, glycosomal enzyme, trypanosoma cruzi
• Biological source: Trypanosoma cruzi (strain CL Brener)
• Total number of polymer chains: 8
• Total formula weight: 279012.88

Authors

Sonani, R.R.,Kurpiewska, K.,Lewinski, K.,Dubin, G. (deposition date: 2021-03-04, release date: 2022-02-16, Last modification date: 2024-01-31)

Primary citation

Sonani, R.R.,Kurpiewska, K.,Lewinski, K.,Dubin, G.
Distinct sequence and structural feature of trypanosoma malate dehydrogenase.
Biochem.Biophys.Res.Commun., 557:288-293, 2021

PubMed Abstract: Glycosomal malate dehydrogenase from Trypanosoma cruzi (tcgMDH) catalyzes the oxidation/reduction of malate/oxaloacetate, a crucial step of the glycolytic process occurring in the glycosome of the human parasite. Inhibition of tcgMDH is considered a druggable trait for the development of trypanocidal drugs. Sequence comparison of MDHs from different organisms revealed a distinct insertion of a prolin rich 9-mer (62-KLPPVPRDP-70) in tcgMDH as compared to other eukaryotic MDHs. Crystal structure of tcgMDH is solved here at 2.6 Å resolution with R/R values of 0.206/0.216. The tcgMDH forms homo-dimer with the solvation free energy (ΔG) gain of -9.77 kcal/mol. The dimeric form is also confirmed in solution by biochemical assays, chemical-crosslinking and dynamic light scattering. The inserted 9-mer adopts a structure of a solvent accessible loop in the vicinity of NAD binding site. The distinct sequence and structural feature of tcgMDH, revealed in the present report, provides an anchor point for the development of inhibitors specific for tcgMDH, possible trypanocidal agents of the future.

PubMed: 33894416
DOI: 10.1016/j.bbrc.2021.04.033

Experimental method

X-RAY DIFFRACTION (2.6 Å)