5YZI

Crystal Structure of Mouse Cytosolic Isocitrate Dehydrogenase complexed with Cadmium

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5YZI の概要

• エントリーDOI: 10.2210/pdb5yzi/pdb
• 分子名称: Isocitrate dehydrogenase [NADP] cytoplasmic, CADMIUM ION, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (4 entities in total)
• 機能のキーワード: idh, oxidoreductase
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 95296.84

構造登録者

Cho, H.J.,Kang, B.S. (登録日: 2017-12-14, 公開日: 2018-07-04, 最終更新日: 2024-03-27)

主引用文献

Cho, H.J.,Cho, H.Y.,Park, J.W.,Kwon, O.S.,Lee, H.S.,Huh, T.L.,Kang, B.S.
NADP+-dependent cytosolic isocitrate dehydrogenase provides NADPH in the presence of cadmium due to the moderate chelating effect of glutathione.
J. Biol. Inorg. Chem., 23:849-860, 2018

PubMed Abstract: Cadmium (Cd) is toxic to living organisms because it causes the malfunction of essential proteins and induces oxidative stress. NADP-dependent cytosolic isocitrate dehydrogenase (IDH) provides reducing energy to counteract oxidative stress via oxidative decarboxylation of isocitrate. Intriguingly, the effects of Cd on the activity of IDH are both positive and negative, and to understand the molecular basis, we determined the crystal structure of NADP-dependent cytosolic IDH in the presence of Cd. The structure includes two Cd ions, one coordinated by active site residues and another near a cysteine residue. Cd presumably inactivates IDH due to its high affinity for thiols, leading to a covalent enzyme modification. However, Cd also activates IDH by providing a divalent cation required for catalytic activity. Inactivation of IDH by Cd is less effective when the enzyme is activated with Cd than Mg. Although reducing agents cannot restore activity following inactivation by Cd, they can maintain IDH activity by chelating Cd. Glutathione, a cellular sulphydryl reductant, has a moderate affinity for Cd, allowing IDH to be activated with residual Cd, unlike dithiothreitol, which has a much higher affinity. In the presence of Cd-consuming cellular antioxidants, cells must continually supply reductants to protect against oxidative stress. The ability of IDH to utilise Cd to generate NADPH could allow cells to protect themselves against Cd.

PubMed: 29923039
DOI: 10.1007/s00775-018-1581-5

実験手法

X-RAY DIFFRACTION (2.519 Å)