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http://purl.uniprot.org/citations/29923039http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29923039http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29923039http://www.w3.org/2000/01/rdf-schema#comment"Cadmium (Cd2+) 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 Cd2+ 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 Cd2+. The structure includes two Cd2+ ions, one coordinated by active site residues and another near a cysteine residue. Cd2+ presumably inactivates IDH due to its high affinity for thiols, leading to a covalent enzyme modification. However, Cd2+ also activates IDH by providing a divalent cation required for catalytic activity. Inactivation of IDH by Cd2+ is less effective when the enzyme is activated with Cd2+ than Mg2+. Although reducing agents cannot restore activity following inactivation by Cd2+, they can maintain IDH activity by chelating Cd2+. Glutathione, a cellular sulphydryl reductant, has a moderate affinity for Cd2+, allowing IDH to be activated with residual Cd2+, unlike dithiothreitol, which has a much higher affinity. In the presence of Cd2+-consuming cellular antioxidants, cells must continually supply reductants to protect against oxidative stress. The ability of IDH to utilise Cd2+ to generate NADPH could allow cells to protect themselves against Cd2+."xsd:string
http://purl.uniprot.org/citations/29923039http://purl.org/dc/terms/identifier"doi:10.1007/s00775-018-1581-5"xsd:string
http://purl.uniprot.org/citations/29923039http://purl.org/dc/terms/identifier"doi:10.1007/s00775-018-1581-5"xsd:string
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/author"Lee H.S."xsd:string
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/author"Lee H.S."xsd:string
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/author"Park J.W."xsd:string
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/author"Park J.W."xsd:string
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/author"Kang B.S."xsd:string
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/author"Kang B.S."xsd:string
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/author"Cho H.J."xsd:string
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/author"Cho H.J."xsd:string
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/author"Cho H.Y."xsd:string
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/author"Cho H.Y."xsd:string
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/author"Kwon O.S."xsd:string
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/author"Kwon O.S."xsd:string
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/author"Huh T.L."xsd:string
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/author"Huh T.L."xsd:string
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/name"J. Biol. Inorg. Chem."xsd:string
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/name"J. Biol. Inorg. Chem."xsd:string
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/pages"849-860"xsd:string
http://purl.uniprot.org/citations/29923039http://purl.uniprot.org/core/pages"849-860"xsd:string