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| | <StructureSection load='6n0m' size='340' side='right'caption='[[6n0m]], [[Resolution|resolution]] 3.30Å' scene=''> | | <StructureSection load='6n0m' size='340' side='right'caption='[[6n0m]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6n0m]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N0M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N0M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6n0m]] is a 5 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=6N0M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6N0M FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K94:4-(difluoromethyl)-L-leucine'>K94</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]] 3.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SESN2, Hi95, SEST2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K94:4-(difluoromethyl)-L-leucine'>K94</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peroxiredoxin Peroxiredoxin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.15 1.11.1.15] </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=6n0m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n0m OCA], [https://pdbe.org/6n0m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6n0m RCSB], [https://www.ebi.ac.uk/pdbsum/6n0m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6n0m ProSAT]</span></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=6n0m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n0m OCA], [http://pdbe.org/6n0m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n0m RCSB], [http://www.ebi.ac.uk/pdbsum/6n0m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n0m ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SESN2_HUMAN SESN2_HUMAN]] Involved in the reduction of peroxiredoxins.<ref>PMID:15105503</ref> | + | [https://www.uniprot.org/uniprot/SESN2_HUMAN SESN2_HUMAN] Involved in the reduction of peroxiredoxins.<ref>PMID:15105503</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Peroxiredoxin]] | + | [[Category: O'Neill D]] |
| - | [[Category: Neill, D O]]
| + | |
| - | [[Category: Amino-acid]]
| + | |
| - | [[Category: Leucine]]
| + | |
| - | [[Category: Mtor]]
| + | |
| - | [[Category: Sensing]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
SESN2_HUMAN Involved in the reduction of peroxiredoxins.[1]
Publication Abstract from PubMed
The mechanistic target of rapamycin complex 1 (mTORC1) has been linked to several important chronic medical conditions many of which are associated with advancing age. A variety of inputs including the amino acid leucine are required for full mTORC1 activation. The cytoplasmic proteins Sestrin1 and Sestrin2 specifically bind to the multiprotein complex GATOR2 and communicate leucine sufficiency to the mTORC1 pathway activation complex. Herein, we report NV-5138, a novel orally bioavailable compound that binds to Sestrin2 and activates mTORC1 both in vitro and in vivo. NV-5138 like leucine transiently activates mTORC1 in several peripheral tissues, but in contrast to leucine uniquely activates this complex in the brain due lack of metabolism and utilization in protein synthesis. As such, NV-5138 will permit the exploration in areas of unmet medical need including neuropsychiatric conditions and cognition which have been linked to the activation status of mTORC1.
Discovery of NV-5138, the first selective Brain mTORC1 activator.,Sengupta S, Giaime E, Narayan S, Hahm S, Howell J, O'Neill D, Vlasuk GP, Saiah E Sci Rep. 2019 Mar 11;9(1):4107. doi: 10.1038/s41598-019-40693-5. PMID:30858438[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Budanov AV, Sablina AA, Feinstein E, Koonin EV, Chumakov PM. Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD. Science. 2004 Apr 23;304(5670):596-600. PMID:15105503 doi:http://dx.doi.org/10.1126/science.1095569
- ↑ Sengupta S, Giaime E, Narayan S, Hahm S, Howell J, O'Neill D, Vlasuk GP, Saiah E. Discovery of NV-5138, the first selective Brain mTORC1 activator. Sci Rep. 2019 Mar 11;9(1):4107. doi: 10.1038/s41598-019-40693-5. PMID:30858438 doi:http://dx.doi.org/10.1038/s41598-019-40693-5
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