7F8R

Crystal structure of human soluble CLIC1 with catalytic cysteine (Cys24) in sulphonic acid form.

7F8R の概要

• エントリーDOI: 10.2210/pdb7f8r/pdb
• 分子名称: Chloride intracellular channel protein 1 (2 entities in total)
• 機能のキーワード: human, chloride intracellular channel 1, clic1, cysteine sulfonic acid, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 54001.36

構造登録者

Kumar, A.,Das, B.K.,Sreeshma, N.S.,Arockiasamy, A. (登録日: 2021-07-02, 公開日: 2022-01-19, 最終更新日: 2023-11-29)

主引用文献

Das, B.K.,Kumar, A.,Sreekumar, S.N.,Ponraj, K.,Gadave, K.,Kumar, S.,Murali Achary, V.M.,Ray, P.,Reddy, M.K.,Arockiasamy, A.
Comparative kinetic analysis of ascorbate (Vitamin-C) recycling dehydroascorbate reductases from plants and humans.
Biochem.Biophys.Res.Commun., 591:110-117, 2021

PubMed Abstract: Ascorbate is an important cellular antioxidant that gets readily oxidized to dehydroascorbate (DHA). Recycling of DHA is therefore paramount in the maintenance of cellular homeostasis and preventing oxidative stress. Dehydroascorbate reductases (DHARs), in conjunction with glutathione (GSH), carry out this vital process in eukaryotes, among which plant DHARs have garnered considerable attention. A detailed kinetic analysis of plant DHARs relative to their human counterparts is, however, lacking. Chloride intracellular channels (HsCLICs) are close homologs of plant DHARs, recently demonstrated to share their enzymatic activity. This study reports the highest turnover rate for a plant DHAR from stress adapted Pennisetum glaucum (PgDHAR). In comparison, HsCLICs 1, 3, and 4 reduced DHA at a significantly lower rate. We further show that the catalytic cysteine from both homologs was susceptible to varying degrees of oxidation, validated by crystal structures and mass-spectrometry. Our findings may have broader implications on crop improvement using pearl millet DHAR vis-à-vis discovery of cancer therapeutics targeting Vitamin-C recycling capability of human CLICs.

PubMed: 35007834
DOI: 10.1016/j.bbrc.2021.12.103

実験手法

X-RAY DIFFRACTION (2.51 Å)