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7p0p
From Proteopedia
(Difference between revisions)
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==NAF-1 bound to M1 molecule== | ==NAF-1 bound to M1 molecule== | ||
| - | <StructureSection load='7p0p' size='340' side='right'caption='[[7p0p]]' scene=''> | + | <StructureSection load='7p0p' size='340' side='right'caption='[[7p0p]], [[Resolution|resolution]] 1.74Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P0P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P0P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7p0p]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P0P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P0P FirstGlance]. <br> |
| - | </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=7p0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p0p OCA], [https://pdbe.org/7p0p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p0p RCSB], [https://www.ebi.ac.uk/pdbsum/7p0p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p0p ProSAT]</span></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]] 1.74Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=49I:2-benzamido-4-[(2~{R})-1,2,3,4-tetrahydronaphthalen-2-yl]thiophene-3-carboxylic+acid'>49I</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene></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=7p0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p0p OCA], [https://pdbe.org/7p0p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p0p RCSB], [https://www.ebi.ac.uk/pdbsum/7p0p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p0p ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/CISD2_HUMAN CISD2_HUMAN] Defects in CISD2 are the cause of Wolfram syndrome type 2 (WFS2) [MIM:[https://omim.org/entry/604928 604928]. A rare disorder characterized by juvenile-onset insulin-dependent diabetes mellitus with optic atrophy. Other manifestations include diabetes insipidus, sensorineural deafness, dementia, psychiatric illnesses. WFS2 patients additionally show a strong bleeding tendency and gastrointestinal ulceration. Diabetes insipidus may be absent.<ref>PMID:17846994</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CISD2_HUMAN CISD2_HUMAN] Regulator of autophagy that contributes to antagonize BECN1-mediated cellular autophagy at the endoplasmic reticulum. Participates in the interaction of BCL2 with BECN1 and is required for BCL2-mediated depression of endoplasmic reticulum Ca(2+) stores during autophagy. Contributes to BIK-initiated autophagy, while it is not involved in BIK-dependent activation of caspases. Involved in life span control, probably via its function as regulator of autophagy.<ref>PMID:17846994</ref> <ref>PMID:20010695</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Elevated levels of mitochondrial iron and reactive oxygen species (ROS) accompany the progression of diabetes, negatively impacting insulin production and secretion from pancreatic cells. In search for a tool to reduce mitochondrial iron and ROS levels, we arrived at a molecule that destabilizes the [2Fe-2S] clusters of NEET proteins (M1). Treatment of db/db diabetic mice with M1 improved hyperglycemia, without the weight gain observed with alternative treatments such as rosiglitazone. The molecular interactions of M1 with the NEET proteins mNT and NAF-1 were determined by X-crystallography. The possibility of controlling diabetes by molecules that destabilize the [2Fe-2S] clusters of NEET proteins, thereby reducing iron-mediated oxidative stress, opens a new route for managing metabolic aberration such as in diabetes. | ||
| + | |||
| + | An anti-diabetic drug targets NEET (CISD) proteins through destabilization of their [2Fe-2S] clusters.,Marjault HB, Karmi O, Zuo K, Michaeli D, Eisenberg-Domovich Y, Rossetti G, de Chassey B, Vonderscher J, Cabantchik I, Carloni P, Mittler R, Livnah O, Meldrum E, Nechushtai R Commun Biol. 2022 May 10;5(1):437. doi: 10.1038/s42003-022-03393-x. PMID:35538231<ref>PMID:35538231</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7p0p" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Eisenberg-Domovich Y]] | [[Category: Eisenberg-Domovich Y]] | ||
Current revision
NAF-1 bound to M1 molecule
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