7F8R
Crystal structure of human soluble CLIC1 with catalytic cysteine (Cys24) in sulphonic acid form.
Summary for 7F8R
Entry DOI | 10.2210/pdb7f8r/pdb |
Descriptor | Chloride intracellular channel protein 1 (2 entities in total) |
Functional Keywords | human, chloride intracellular channel 1, clic1, cysteine sulfonic acid, oxidoreductase |
Biological source | Homo sapiens (Human) |
Total number of polymer chains | 2 |
Total formula weight | 54001.36 |
Authors | Kumar, A.,Das, B.K.,Sreeshma, N.S.,Arockiasamy, A. (deposition date: 2021-07-02, release date: 2022-01-19, Last modification date: 2023-11-29) |
Primary citation | 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 Cited by 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: 35007834DOI: 10.1016/j.bbrc.2021.12.103 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.51 Å) |
Structure validation
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