7NRZ

Crystal structure of malate dehydrogenase from Trypanosoma cruzi

7NRZ の概要

• エントリーDOI: 10.2210/pdb7nrz/pdb
• 分子名称: Malate dehydrogenase, 1,2-ETHANEDIOL, DI(HYDROXYETHYL)ETHER, ... (7 entities in total)
• 機能のキーワード: oxidoreductase, glycosomal enzyme, trypanosoma cruzi
• 由来する生物種: Trypanosoma cruzi (strain CL Brener)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 279012.88

構造登録者

Sonani, R.R.,Kurpiewska, K.,Lewinski, K.,Dubin, G. (登録日: 2021-03-04, 公開日: 2022-02-16, 最終更新日: 2024-01-31)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.6 Å)