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==Crystal Structure of Mouse Cytosolic Isocitrate Dehydrogenase complexed with Cadmium==
==Crystal Structure of Mouse Cytosolic Isocitrate Dehydrogenase complexed with Cadmium==
<StructureSection load='5yzi' size='340' side='right' caption='[[5yzi]], [[Resolution|resolution]] 2.52&Aring;' scene=''>
<StructureSection load='5yzi' size='340' side='right'caption='[[5yzi]], [[Resolution|resolution]] 2.52&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5yzi]] is a 2 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2cmv 2cmv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YZI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YZI FirstGlance]. <br>
<table><tr><td colspan='2'>[[5yzi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2cmv 2cmv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YZI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YZI FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.519&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Isocitrate_dehydrogenase_(NADP(+)) Isocitrate dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.42 1.1.1.42] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5yzi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yzi OCA], [http://pdbe.org/5yzi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yzi RCSB], [http://www.ebi.ac.uk/pdbsum/5yzi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yzi ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5yzi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yzi OCA], [https://pdbe.org/5yzi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yzi RCSB], [https://www.ebi.ac.uk/pdbsum/5yzi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yzi ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/IDHC_MOUSE IDHC_MOUSE]
Cadmium (Cd(2+)) 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(2+) 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(2+). The structure includes two Cd(2+) ions, one coordinated by active site residues and another near a cysteine residue. Cd(2+) presumably inactivates IDH due to its high affinity for thiols, leading to a covalent enzyme modification. However, Cd(2+) also activates IDH by providing a divalent cation required for catalytic activity. Inactivation of IDH by Cd(2+) is less effective when the enzyme is activated with Cd(2+) than Mg(2+). Although reducing agents cannot restore activity following inactivation by Cd(2+), they can maintain IDH activity by chelating Cd(2+). Glutathione, a cellular sulphydryl reductant, has a moderate affinity for Cd(2+), allowing IDH to be activated with residual Cd(2+), unlike dithiothreitol, which has a much higher affinity. In the presence of Cd(2+)-consuming cellular antioxidants, cells must continually supply reductants to protect against oxidative stress. The ability of IDH to utilise Cd(2+) to generate NADPH could allow cells to protect themselves against Cd(2+).
 
NADP(+)-dependent cytosolic isocitrate dehydrogenase provides NADPH in the presence of cadmium due to the moderate chelating effect of glutathione.,Cho HJ, Cho HY, Park JW, Kwon OS, Lee HS, Huh TL, Kang BS J Biol Inorg Chem. 2018 Jun 19. pii: 10.1007/s00775-018-1581-5. doi:, 10.1007/s00775-018-1581-5. PMID:29923039<ref>PMID:29923039</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5yzi" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Isocitrate dehydrogenase|Isocitrate dehydrogenase]]
*[[Isocitrate dehydrogenase 3D structures|Isocitrate dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Cho, H J]]
[[Category: Large Structures]]
[[Category: Kang, B S]]
[[Category: Mus musculus]]
[[Category: Idh]]
[[Category: Cho HJ]]
[[Category: Oxidoreductase]]
[[Category: Kang BS]]

Latest revision as of 13:25, 27 March 2024

Crystal Structure of Mouse Cytosolic Isocitrate Dehydrogenase complexed with CadmiumCrystal Structure of Mouse Cytosolic Isocitrate Dehydrogenase complexed with Cadmium

Structural highlights

5yzi is a 2 chain structure with sequence from Mus musculus. This structure supersedes the now removed PDB entry 2cmv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.519Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IDHC_MOUSE

See Also

5yzi, resolution 2.52Å

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