3jbz - Revision history

OCA at 08:43, 7 February 2024

2024-02-07T08:43:32Z

←Older revision		Revision as of 08:43, 7 February 2024
Line 3:		Line 3:
	<SX load='3jbz' size='340' side='right' viewer='molstar' caption='[[3jbz]], [[Resolution\|resolution]] 28.00Å' scene=''>		<SX load='3jbz' size='340' side='right' viewer='molstar' caption='[[3jbz]], [[Resolution\|resolution]] 28.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3jbz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JBZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JBZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3jbz]] is a 1 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=3JBZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JBZ FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>~~, ~~<scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MGF:TRIFLUOROMAGNESATE'>MGF</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 28Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~FRAP, FRAP1, FRAP2, MTOR, RAFT1, RAPT1 ([https://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=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MGF:TRIFLUOROMAGNESATE'>MGF</scene></td></tr>
-	<~~tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </~~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=3jbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jbz OCA], [https://pdbe.org/3jbz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jbz RCSB], [https://www.ebi.ac.uk/pdbsum/3jbz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jbz 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=3jbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jbz OCA], [https://pdbe.org/3jbz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jbz RCSB], [https://www.ebi.ac.uk/pdbsum/3jbz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jbz ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/MTOR_HUMAN MTOR_HUMAN]] Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B and the inhibitor of translation initiation PDCD4. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 a RNA polymerase III-repressor. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. mTORC1 also negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules. As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. Plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'.<ref>PMID:12150925</ref> <ref>PMID:12150926</ref> <ref>PMID:12231510</ref> <ref>PMID:12087098</ref> <ref>PMID:14651849</ref> <ref>PMID:12718876</ref> <ref>PMID:15268862</ref> <ref>PMID:15545625</ref> <ref>PMID:15467718</ref> <ref>PMID:15718470</ref> <ref>PMID:18925875</ref> <ref>PMID:18762023</ref> <ref>PMID:18497260</ref> <ref>PMID:20537536</ref> <ref>PMID:20516213</ref> <ref>PMID:21659604</ref>	+	[https://www.uniprot.org/uniprot/MTOR_HUMAN MTOR_HUMAN] Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B and the inhibitor of translation initiation PDCD4. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 a RNA polymerase III-repressor. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. mTORC1 also negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules. As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. Plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'.<ref>PMID:12150925</ref> <ref>PMID:12150926</ref> <ref>PMID:12231510</ref> <ref>PMID:12087098</ref> <ref>PMID:14651849</ref> <ref>PMID:12718876</ref> <ref>PMID:15268862</ref> <ref>PMID:15545625</ref> <ref>PMID:15467718</ref> <ref>PMID:15718470</ref> <ref>PMID:18925875</ref> <ref>PMID:18762023</ref> <ref>PMID:18497260</ref> <ref>PMID:20537536</ref> <ref>PMID:20516213</ref> <ref>PMID:21659604</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	DNA-double strand breaks activate the serine/threonine protein kinase ataxia-telangiectasia mutated (ATM) to initiate DNA damage signal transduction. This activation process involves autophosphorylation and dissociation of inert ATM dimers into monomers that are catalytically active. Using single-particle electron microscopy (EM), we determined the structure of dimeric ATM in its resting state. The EM map could accommodate the crystal structure of the N-terminal truncated mammalian target of rapamycin (mTOR), a closely related enzyme of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family, allowing for the localization of the N- and the C-terminal regions of ATM. In the dimeric structure, the actives sites are buried, restricting the access of the substrates to these sites. The unanticipated domain organization of ATM provides a basis for understanding its mechanism of inhibition.	+
-		+
-	~~Structure of the human dimeric ATM kinase.,Lau WC, Li Y, Liu Z, Gao Y, Zhang Q, Huen MS Cell Cycle. 2016;15(8):1117-24. doi: 10.1080/15384101.2016.1158362. PMID:27097373<ref>PMID:27097373</ref>~~	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3jbz" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</SX>		</SX>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Lau WCY]]
-	[[Category: Lau~~, W C.Y]]~~	+
-	~~[[Category: Mtor]]~~	+
-	~~[[Category: Pikk]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 13:31, 4 May 2022

2022-05-04T13:31:39Z

←Older revision		Revision as of 13:31, 4 May 2022
Line 3:		Line 3:
	<SX load='3jbz' size='340' side='right' viewer='molstar' caption='[[3jbz]], [[Resolution\|resolution]] 28.00Å' scene=''>		<SX load='3jbz' size='340' side='right' viewer='molstar' caption='[[3jbz]], [[Resolution\|resolution]] 28.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3jbz]] is a 1 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=3JBZ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=3JBZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3jbz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JBZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JBZ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MGF:TRIFLUOROMAGNESATE'>MGF</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MGF:TRIFLUOROMAGNESATE'>MGF</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FRAP, FRAP1, FRAP2, MTOR, RAFT1, RAPT1 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FRAP, FRAP1, FRAP2, MTOR, RAFT1, RAPT1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></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=3jbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jbz OCA], [~~http~~://pdbe.org/3jbz PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3jbz RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3jbz PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3jbz 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=3jbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jbz OCA], [https://pdbe.org/3jbz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jbz RCSB], [https://www.ebi.ac.uk/pdbsum/3jbz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jbz ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/MTOR_HUMAN MTOR_HUMAN]] Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B and the inhibitor of translation initiation PDCD4. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 a RNA polymerase III-repressor. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. mTORC1 also negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules. As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. Plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'.<ref>PMID:12150925</ref> <ref>PMID:12150926</ref> <ref>PMID:12231510</ref> <ref>PMID:12087098</ref> <ref>PMID:14651849</ref> <ref>PMID:12718876</ref> <ref>PMID:15268862</ref> <ref>PMID:15545625</ref> <ref>PMID:15467718</ref> <ref>PMID:15718470</ref> <ref>PMID:18925875</ref> <ref>PMID:18762023</ref> <ref>PMID:18497260</ref> <ref>PMID:20537536</ref> <ref>PMID:20516213</ref> <ref>PMID:21659604</ref>	+	[[https://www.uniprot.org/uniprot/MTOR_HUMAN MTOR_HUMAN]] Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B and the inhibitor of translation initiation PDCD4. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 a RNA polymerase III-repressor. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. mTORC1 also negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules. As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. Plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'.<ref>PMID:12150925</ref> <ref>PMID:12150926</ref> <ref>PMID:12231510</ref> <ref>PMID:12087098</ref> <ref>PMID:14651849</ref> <ref>PMID:12718876</ref> <ref>PMID:15268862</ref> <ref>PMID:15545625</ref> <ref>PMID:15467718</ref> <ref>PMID:15718470</ref> <ref>PMID:18925875</ref> <ref>PMID:18762023</ref> <ref>PMID:18497260</ref> <ref>PMID:20537536</ref> <ref>PMID:20516213</ref> <ref>PMID:21659604</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 18:30, 10 April 2020

2020-04-10T18:30:52Z

←Older revision		Revision as of 18:30, 10 April 2020
Line 3:		Line 3:
	<SX load='3jbz' size='340' side='right' viewer='molstar' caption='[[3jbz]], [[Resolution\|resolution]] 28.00Å' scene=''>		<SX load='3jbz' size='340' side='right' viewer='molstar' caption='[[3jbz]], [[Resolution\|resolution]] 28.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3jbz]] is a 1 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=3JBZ OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3JBZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3jbz]] is a 1 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=3JBZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3JBZ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MGF:TRIFLUOROMAGNESATE'>MGF</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MGF:TRIFLUOROMAGNESATE'>MGF</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FRAP, FRAP1, FRAP2, MTOR, RAFT1, RAPT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FRAP, FRAP1, FRAP2, MTOR, RAFT1, RAPT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=3jbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jbz OCA], [http://pdbe.org/3jbz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jbz RCSB], [http://www.ebi.ac.uk/pdbsum/3jbz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3jbz ProSAT]</span></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=3jbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jbz OCA], [http://pdbe.org/3jbz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jbz RCSB], [http://www.ebi.ac.uk/pdbsum/3jbz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3jbz ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 17:39, 6 March 2020

2020-03-06T17:39:31Z

←Older revision		Revision as of 17:39, 6 March 2020
Line 1:		Line 1:

	==Crystal structure of mTOR docked into EM map of dimeric ATM kinase==		==Crystal structure of mTOR docked into EM map of dimeric ATM kinase==
-	<~~StructureSection~~ load='3jbz' size='340' side='right'caption='[[3jbz]], [[Resolution\|resolution]] 28.00Å' scene=''>	+	<SX load='3jbz' size='340' side='right' viewer='molstar' caption='[[3jbz]], [[Resolution\|resolution]] 28.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3jbz]] is a 1 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=3JBZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JBZ FirstGlance]. <br>		<table><tr><td colspan='2'>[[3jbz]] is a 1 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=3JBZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JBZ FirstGlance]. <br>
Line 23:		Line 23:
	<references/>		<references/>
	__TOC__		__TOC__
-	</~~StructureSection~~>	+	</SX>
	[[Category: Human]]		[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]

OCA at 05:40, 10 October 2019

2019-10-10T05:40:42Z

←Older revision		Revision as of 05:40, 10 October 2019
Line 1:		Line 1:

	==Crystal structure of mTOR docked into EM map of dimeric ATM kinase==		==Crystal structure of mTOR docked into EM map of dimeric ATM kinase==
-	<StructureSection load='3jbz' size='340' side='right' caption='[[3jbz]], [[Resolution\|resolution]] 28.00Å' scene=''>	+	<StructureSection load='3jbz' size='340' side='right'caption='[[3jbz]], [[Resolution\|resolution]] 28.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3jbz]] is a 1 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=3JBZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JBZ FirstGlance]. <br>		<table><tr><td colspan='2'>[[3jbz]] is a 1 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=3JBZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JBZ FirstGlance]. <br>
Line 25:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Lau, W C.Y]]		[[Category: Lau, W C.Y]]

OCA at 09:19, 19 December 2018

2018-12-19T09:19:44Z

←Older revision		Revision as of 09:19, 19 December 2018
Line 3:		Line 3:
	<StructureSection load='3jbz' size='340' side='right' caption='[[3jbz]], [[Resolution\|resolution]] 28.00Å' scene=''>		<StructureSection load='3jbz' size='340' side='right' caption='[[3jbz]], [[Resolution\|resolution]] 28.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3jbz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JBZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JBZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3jbz]] is a 1 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=3JBZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JBZ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MGF:TRIFLUOROMAGNESATE'>MGF</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MGF:TRIFLUOROMAGNESATE'>MGF</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FRAP, FRAP1, FRAP2, MTOR, RAFT1, RAPT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=3jbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jbz OCA], [http://pdbe.org/3jbz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jbz RCSB], [http://www.ebi.ac.uk/pdbsum/3jbz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3jbz 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=3jbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jbz OCA], [http://pdbe.org/3jbz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jbz RCSB], [http://www.ebi.ac.uk/pdbsum/3jbz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3jbz ProSAT]</span></td></tr>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Lau, W C.Y]]		[[Category: Lau, W C.Y]]

OCA at 03:20, 10 December 2016

2016-12-10T03:20:03Z

←Older revision		Revision as of 03:20, 10 December 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 3jbz is ~~ON HOLD~~	+	==Crystal structure of mTOR docked into EM map of dimeric ATM kinase==
		+	<StructureSection load='3jbz' size='340' side='right' caption='[[3jbz]], [[Resolution\|resolution]] 28.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3jbz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JBZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JBZ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MGF:TRIFLUOROMAGNESATE'>MGF</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=3jbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jbz OCA], [http://pdbe.org/3jbz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jbz RCSB], [http://www.ebi.ac.uk/pdbsum/3jbz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3jbz ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MTOR_HUMAN MTOR_HUMAN]] Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B and the inhibitor of translation initiation PDCD4. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 a RNA polymerase III-repressor. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. mTORC1 also negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules. As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. Plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'.<ref>PMID:12150925</ref> <ref>PMID:12150926</ref> <ref>PMID:12231510</ref> <ref>PMID:12087098</ref> <ref>PMID:14651849</ref> <ref>PMID:12718876</ref> <ref>PMID:15268862</ref> <ref>PMID:15545625</ref> <ref>PMID:15467718</ref> <ref>PMID:15718470</ref> <ref>PMID:18925875</ref> <ref>PMID:18762023</ref> <ref>PMID:18497260</ref> <ref>PMID:20537536</ref> <ref>PMID:20516213</ref> <ref>PMID:21659604</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	DNA-double strand breaks activate the serine/threonine protein kinase ataxia-telangiectasia mutated (ATM) to initiate DNA damage signal transduction. This activation process involves autophosphorylation and dissociation of inert ATM dimers into monomers that are catalytically active. Using single-particle electron microscopy (EM), we determined the structure of dimeric ATM in its resting state. The EM map could accommodate the crystal structure of the N-terminal truncated mammalian target of rapamycin (mTOR), a closely related enzyme of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family, allowing for the localization of the N- and the C-terminal regions of ATM. In the dimeric structure, the actives sites are buried, restricting the access of the substrates to these sites. The unanticipated domain organization of ATM provides a basis for understanding its mechanism of inhibition.

-	~~Authors:~~ Lau, W.C.Y.	+	Structure of the human dimeric ATM kinase.,Lau WC, Li Y, Liu Z, Gao Y, Zhang Q, Huen MS Cell Cycle. 2016;15(8):1117-24. doi: 10.1080/15384101.2016.1158362. PMID:27097373<ref>PMID:27097373</ref>

-	~~Description: Crystal structure~~ of ~~mTOR docked into EM map~~ of ~~dimeric ATM kinase~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Lau, W.C.Y]]	+	<div class="pdbe-citations 3jbz" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Lau, W C.Y]]
		+	[[Category: Mtor]]
		+	[[Category: Pikk]]
		+	[[Category: Transferase]]

OCA: Protected "3jbz" [edit=sysop:move=sysop]

2015-11-30T22:40:11Z

Protected "3jbz" [edit=sysop:move=sysop]

←Older revision

Revision as of 22:40, 30 November 2015

OCA: New page: '''Unreleased structure''' The entry 3jbz is ON HOLD Authors: Lau, W.C.Y. Description: Crystal structure of mTOR docked into EM map of dimeric ATM kinase [[Category: Unreleased Structu...

2015-11-30T22:40:10Z

New page: '''Unreleased structure''' The entry 3jbz is ON HOLD Authors: Lau, W.C.Y. Description: Crystal structure of mTOR docked into EM map of dimeric ATM kinase [[Category: Unreleased Structu...

New page

'''Unreleased structure'''

The entry 3jbz is ON HOLD

Authors: Lau, W.C.Y.

Description: Crystal structure of mTOR docked into EM map of dimeric ATM kinase
[[Category: Unreleased Structures]]
[[Category: Lau, W.C.Y]]