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| | <StructureSection load='6ssh' size='340' side='right'caption='[[6ssh]], [[Resolution|resolution]] 1.40Å' scene=''> | | <StructureSection load='6ssh' size='340' side='right'caption='[[6ssh]], [[Resolution|resolution]] 1.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ssh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Cbs_144.50 Cbs 144.50]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SSH OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6SSH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ssh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Chaetomium_thermophilum Chaetomium thermophilum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SSH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SSH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 1.4Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CTHT_0061860 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=209285 CBS 144.50])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ssh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ssh OCA], [http://pdbe.org/6ssh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ssh RCSB], [http://www.ebi.ac.uk/pdbsum/6ssh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ssh 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=6ssh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ssh OCA], [https://pdbe.org/6ssh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ssh RCSB], [https://www.ebi.ac.uk/pdbsum/6ssh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ssh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/G0SFF5_CHATD G0SFF5_CHATD] |
| | <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: Cbs 144 50]] | + | [[Category: Chaetomium thermophilum]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hansmann, P]] | + | [[Category: Hansmann P]] |
| - | [[Category: Kiontke, S]] | + | [[Category: Kiontke S]] |
| - | [[Category: Kummel, D]] | + | [[Category: Kummel D]] |
| - | [[Category: Gtpase activating protein]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
G0SFF5_CHATD
Publication Abstract from PubMed
The TSC complex is the cognate GTPase-activating protein (GAP) for the small GTPase Rheb and a crucial regulator of the mechanistic target of rapamycin complex 1 (mTORC1). Mutations in the TSC1 and TSC2 subunits of the complex cause tuberous sclerosis complex (TSC). We present the crystal structure of the catalytic asparagine-thumb GAP domain of TSC2. A model of the TSC2-Rheb complex and molecular dynamics simulations suggest that TSC2 Asn1643 and Rheb Tyr35 are key active site residues, while Rheb Arg15 and Asp65, previously proposed as catalytic residues, contribute to the TSC2-Rheb interface and indirectly aid catalysis. The TSC2 GAP domain is further stabilized by interactions with other TSC2 domains. We characterize TSC2 variants that partially affect TSC2 functionality and are associated with atypical symptoms in patients, suggesting that mutations in TSC1 and TSC2 might predispose to neurological and vascular disorders without fulfilling the clinical criteria for TSC.
Structure of the TSC2 GAP Domain: Mechanistic Insight into Catalysis and Pathogenic Mutations.,Hansmann P, Bruckner A, Kiontke S, Berkenfeld B, Seebohm G, Brouillard P, Vikkula M, Jansen FE, Nellist M, Oeckinghaus A, Kummel D Structure. 2020 Jun 4. pii: S0969-2126(20)30177-5. doi:, 10.1016/j.str.2020.05.008. PMID:32502382[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hansmann P, Bruckner A, Kiontke S, Berkenfeld B, Seebohm G, Brouillard P, Vikkula M, Jansen FE, Nellist M, Oeckinghaus A, Kummel D. Structure of the TSC2 GAP Domain: Mechanistic Insight into Catalysis and Pathogenic Mutations. Structure. 2020 Jun 4. pii: S0969-2126(20)30177-5. doi:, 10.1016/j.str.2020.05.008. PMID:32502382 doi:http://dx.doi.org/10.1016/j.str.2020.05.008
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