4fap - Revision history

OCA at 15:20, 14 March 2024

2024-03-14T15:20:14Z

←Older revision		Revision as of 15:20, 14 March 2024
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		+
	==ATOMIC STRUCTURES OF THE RAPAMYCIN ANALOGS IN COMPLEX WITH BOTH HUMAN FKBP12 AND FRB DOMAIN OF FRAP==		==ATOMIC STRUCTURES OF THE RAPAMYCIN ANALOGS IN COMPLEX WITH BOTH HUMAN FKBP12 AND FRB DOMAIN OF FRAP==
-	<StructureSection load='4fap' size='340' side='right' caption='[[4fap]], [[Resolution\|resolution]] 2.80Å' scene=''>	+	<StructureSection load='4fap' size='340' side='right'caption='[[4fap]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4fap]] is a 2 chain structure with sequence from [~~http://en.wikipedia.org/wiki/Human Human] and [http~~://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FAP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4FAP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4fap]] is a 2 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=4FAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FAP FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=ARD:C15-(R)-METHYLTHIENYL+RAPAMYCIN'>ARD</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]] 2.8Å</td></tr>
-	~~<tr~~ id~~='related'><td class~~="~~sblockLbl~~">~~<b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2fap\|2fap]]~~, [[~~3fap~~\|~~3fap~~]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ARD:C15-(R)-METHYLTHIENYL+RAPAMYCIN'>ARD</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>HUMAN HIPPOCAMPAL CDNA LIBRARY SOURCE 8 (CLONTECH, PALO ALTO, CA) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9606 HUMAN])</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=4fap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fap OCA], [https://pdbe.org/4fap PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fap RCSB], [https://www.ebi.ac.uk/pdbsum/4fap PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fap ProSAT]</span></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks~~'>~~[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8]~~ </~~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=4fap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fap OCA], [~~http~~://pdbe.org/4fap PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4fap RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4fap PDBsum]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/FKB1A_HUMAN FKB1A_HUMAN]] Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruites SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.<ref>PMID:9233797</ref> <ref>PMID:16720724</ref> [[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/FKB1A_HUMAN FKB1A_HUMAN] Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruites SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.<ref>PMID:9233797</ref> <ref>PMID:16720724</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fa/4fap_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fa/4fap_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 21:		Line 20:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=4fap ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=4fap ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The structure of the FKBP12-rapamycin-FRB ternary complex has now been refined at 2.2 A resolution. The cell-cycle arrest agent rapamycin binds FK506-binding protein (FKBP12) and the FKBP12-rapamycin binding (FRB) domain of FKBP12-rapamycin associated protein (FRAP) simultaneously, and the inhibition of FRAP is responsible for rapamycin's biological activity. The conformation of rapamycin in the ternary complex is very similar to that observed in the FKBP12-rapamycin binary complex, with an r.m.s. difference of only 0.30 A. However, a slight (9 degrees ) rotation repositions the FRB-binding face of rapamycin in the ternary complex. There are extensive rapamycin-protein interactions and relatively few interactions between the two protein partners FKBP12 and FRB, these interactions mainly involving residues in the 40s and 80s loops of FKBP12 and alpha1 and alpha4 of FRB. The high-resolution refinement has revealed the crucial role of several buried waters in the formation of the ternary complex.
-
-	Refined structure of the FKBP12-rapamycin-FRB ternary complex at 2.2 A resolution.,Liang J, Choi J, Clardy J Acta Crystallogr D Biol Crystallogr. 1999 Apr;55(Pt 4):736-44. PMID:10089303<ref>PMID:10089303</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4fap" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
-	*[[~~FK506 binding protein~~\|~~FK506 binding protein~~]]	+	*[[FKBP 3D structures\|FKBP 3D structures]]
-	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]	+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 39:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: ~~Human]]~~	+	[[Category: Large Structures]]
-	~~[[Category: Peptidylprolyl isomerase~~]]	+	[[Category: Clardy J]]
-	[[Category: Clardy, J]]	+	[[Category: Liang J]]
-	[[Category: Liang, J]]	+
-	~~[[Category: Cell cycle]]~~	+
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Fkbp12]]~~	+
-	~~[[Category: Frap]]~~	+
-	~~[[Category: Gene therapy]]~~	+
-	~~[[Category: Rapamycin~~]]	+

OCA at 06:28, 9 February 2016

2016-02-09T06:28:21Z

←Older revision		Revision as of 06:28, 9 February 2016
Line 2:		Line 2:
	<StructureSection load='4fap' size='340' side='right' caption='[[4fap]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='4fap' size='340' side='right' caption='[[4fap]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4fap]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FAP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FAP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4fap]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FAP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FAP FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ARD:C15-(R)-METHYLTHIENYL+RAPAMYCIN'>ARD</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ARD:C15-(R)-METHYLTHIENYL+RAPAMYCIN'>ARD</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2fap\|2fap]], [[3fap\|3fap]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2fap\|2fap]], [[3fap\|3fap]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HUMAN HIPPOCAMPAL CDNA LIBRARY SOURCE 8 (CLONTECH, PALO ALTO, CA) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HUMAN HIPPOCAMPAL CDNA LIBRARY SOURCE 8 (CLONTECH, PALO ALTO, CA) ([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/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </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=4fap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fap OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fap RCSB], [http://www.ebi.ac.uk/pdbsum/4fap PDBsum]</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=4fap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fap OCA], [http://pdbe.org/4fap PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fap RCSB], [http://www.ebi.ac.uk/pdbsum/4fap PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[http://www.uniprot.org/uniprot/FKB1A_HUMAN FKB1A_HUMAN]] Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruites SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.<ref>PMID:9233797</ref> <ref>PMID:16720724</ref> [[http://www.uniprot.org/uniprot/~~FRAP_HUMAN FRAP_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>	+	[[http://www.uniprot.org/uniprot/FKB1A_HUMAN FKB1A_HUMAN]] Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruites SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.<ref>PMID:9233797</ref> <ref>PMID:16720724</ref> [[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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=4fap ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 29:		Line 29:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4fap" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[FK506 binding protein\|FK506 binding protein]]		*[[FK506 binding protein\|FK506 binding protein]]
		+	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
	== References ==		== References ==
	<references/>		<references/>
Line 37:		Line 39:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
		+	[[Category: Human]]
	[[Category: Peptidylprolyl isomerase]]		[[Category: Peptidylprolyl isomerase]]
	[[Category: Clardy, J]]		[[Category: Clardy, J]]

OCA at 05:02, 25 December 2014

2014-12-25T05:02:20Z

←Older revision		Revision as of 05:02, 25 December 2014
Line 9:		Line 9:
	<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=4fap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fap OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fap RCSB], [http://www.ebi.ac.uk/pdbsum/4fap PDBsum]</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=4fap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fap OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fap RCSB], [http://www.ebi.ac.uk/pdbsum/4fap PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/FKB1A_HUMAN FKB1A_HUMAN]] Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruites SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.<ref>PMID:9233797</ref> <ref>PMID:16720724</ref> [[http://www.uniprot.org/uniprot/FRAP_HUMAN FRAP_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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 15:40, 9 December 2014

2014-12-09T15:40:48Z

←Older revision		Revision as of 15:40, 9 December 2014
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-	[[~~Image:~~4fap.~~png~~\|~~left~~\|200px]]	+	==ATOMIC STRUCTURES OF THE RAPAMYCIN ANALOGS IN COMPLEX WITH BOTH HUMAN FKBP12 AND FRB DOMAIN OF FRAP==
		+	<StructureSection load='4fap' size='340' side='right' caption='[[4fap]], [[Resolution\|resolution]] 2.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4fap]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FAP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FAP FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ARD:C15-(R)-METHYLTHIENYL+RAPAMYCIN'>ARD</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2fap\|2fap]], [[3fap\|3fap]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HUMAN HIPPOCAMPAL CDNA LIBRARY SOURCE 8 (CLONTECH, PALO ALTO, CA) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </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=4fap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fap OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fap RCSB], [http://www.ebi.ac.uk/pdbsum/4fap PDBsum]</span></td></tr>
		+	</table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fa/4fap_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The structure of the FKBP12-rapamycin-FRB ternary complex has now been refined at 2.2 A resolution. The cell-cycle arrest agent rapamycin binds FK506-binding protein (FKBP12) and the FKBP12-rapamycin binding (FRB) domain of FKBP12-rapamycin associated protein (FRAP) simultaneously, and the inhibition of FRAP is responsible for rapamycin's biological activity. The conformation of rapamycin in the ternary complex is very similar to that observed in the FKBP12-rapamycin binary complex, with an r.m.s. difference of only 0.30 A. However, a slight (9 degrees ) rotation repositions the FRB-binding face of rapamycin in the ternary complex. There are extensive rapamycin-protein interactions and relatively few interactions between the two protein partners FKBP12 and FRB, these interactions mainly involving residues in the 40s and 80s loops of FKBP12 and alpha1 and alpha4 of FRB. The high-resolution refinement has revealed the crucial role of several buried waters in the formation of the ternary complex.

-	~~{{STRUCTURE_4fap\| PDB=4fap \| SCENE= }}~~	+	Refined structure of the FKBP12-rapamycin-FRB ternary complex at 2.2 A resolution.,Liang J, Choi J, Clardy J Acta Crystallogr D Biol Crystallogr. 1999 Apr;55(Pt 4):736-44. PMID:10089303<ref>PMID:10089303</ref>

-	~~===ATOMIC STRUCTURES OF THE RAPAMYCIN ANALOGS IN COMPLEX WITH BOTH HUMAN FKBP12 AND FRB DOMAIN OF FRAP===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_10089303}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[4fap]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=4FAP OCA].~~	+

	==See Also==		==See Also==
	*[[FK506 binding protein\|FK506 binding protein]]		*[[FK506 binding protein\|FK506 binding protein]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:010089303<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Peptidylprolyl isomerase]]		[[Category: Peptidylprolyl isomerase]]
-	[[Category: Clardy, J.]]	+	[[Category: Clardy, J]]
-	[[Category: Liang, J.]]	+	[[Category: Liang, J]]
	[[Category: Cell cycle]]		[[Category: Cell cycle]]
	[[Category: Complex]]		[[Category: Complex]]

OCA at 12:57, 20 October 2012

2012-10-20T12:57:55Z

←Older revision		Revision as of 12:57, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[4fap]] is a 2 chain structure ~~of [[FK506 binding protein]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FAP OCA].	+	[[4fap]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FAP OCA].

	==See Also==		==See Also==

OCA: Protected "4fap" [edit=sysop:move=sysop]

2012-07-26T10:28:39Z

Protected "4fap" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:28, 26 July 2012

OCA at 10:28, 26 July 2012

2012-07-26T10:28:37Z

←Older revision		Revision as of 10:28, 26 July 2012
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-	{{Seed}}
	[[Image:4fap.png\|left\|200px]]		[[Image:4fap.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_4fap", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_4fap\| PDB=4fap \| SCENE= }}		{{STRUCTURE_4fap\| PDB=4fap \| SCENE= }}

	===ATOMIC STRUCTURES OF THE RAPAMYCIN ANALOGS IN COMPLEX WITH BOTH HUMAN FKBP12 AND FRB DOMAIN OF FRAP===		===ATOMIC STRUCTURES OF THE RAPAMYCIN ANALOGS IN COMPLEX WITH BOTH HUMAN FKBP12 AND FRB DOMAIN OF FRAP===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_10089303}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 10089303 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_10089303}}		{{ABSTRACT_PUBMED_10089303}}

	==About this Structure==		==About this Structure==
-	~~4FAP~~ is a 2 ~~chains~~ structure of ~~sequences~~ from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FAP OCA].	+	[[4fap]] is a 2 chain structure of [[FK506 binding protein]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FAP OCA].
		+
		+	==See Also==
		+	*[[FK506 binding protein\|FK506 binding protein]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~10089303~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:010089303</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Peptidylprolyl isomerase]]		[[Category: Peptidylprolyl isomerase]]
	[[Category: Clardy, J.]]		[[Category: Clardy, J.]]
	[[Category: Liang, J.]]		[[Category: Liang, J.]]
		+	[[Category: Cell cycle]]
	[[Category: Complex]]		[[Category: Complex]]
	[[Category: Fkbp12]]		[[Category: Fkbp12]]
Line 33:		Line 25:
	[[Category: Gene therapy]]		[[Category: Gene therapy]]
	[[Category: Rapamycin]]		[[Category: Rapamycin]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 07:13:39 2009''

OCA at 05:13, 17 February 2009

2009-02-17T05:13:42Z

←Older revision		Revision as of 05:13, 17 February 2009
Line 20:		Line 20:

	==About this Structure==		==About this Structure==
-	4FAP is a ~~[[Protein complex]]~~ structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FAP OCA].	+	4FAP is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FAP OCA].

	==Reference==		==Reference==
-	~~Refined structure of the FKBP12-rapamycin-FRB ternary complex at 2.2 A resolution., Liang J, Choi J, Clardy J, Acta Crystallogr D Biol Crystallogr. 1999 Apr;55(Pt 4):736-44.~~ PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/10089303 10089303]~~	+	<ref group="xtra">PMID:10089303</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Peptidylprolyl isomerase]]		[[Category: Peptidylprolyl isomerase]]
-	[[Category: Protein complex]]
	[[Category: Clardy, J.]]		[[Category: Clardy, J.]]
	[[Category: Liang, J.]]		[[Category: Liang, J.]]
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	[[Category: Rapamycin]]		[[Category: Rapamycin]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Thu Jul 3 13~~:36:39 ~~2008~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 07:13:39 2009''

OCA at 10:36, 3 July 2008

2008-07-03T10:36:39Z

←Older revision		Revision as of 10:36, 3 July 2008
Line 1:		Line 1:
-	[[Image:4fap.~~gif~~\|left\|200px]]	+	{{Seed}}
		+	[[Image:4fap.png\|left\|200px]]

	<!--		<!--
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	{{STRUCTURE_4fap\| PDB=4fap \| SCENE= }}		{{STRUCTURE_4fap\| PDB=4fap \| SCENE= }}

-	~~'''~~ATOMIC STRUCTURES OF THE RAPAMYCIN ANALOGS IN COMPLEX WITH BOTH HUMAN FKBP12 AND FRB DOMAIN OF FRAP~~'''~~	+	===ATOMIC STRUCTURES OF THE RAPAMYCIN ANALOGS IN COMPLEX WITH BOTH HUMAN FKBP12 AND FRB DOMAIN OF FRAP===


-	~~==Overview==~~	+	<!--
-	~~The structure of the FKBP12~~-~~rapamycin~~-~~FRB ternary complex has now been refined at 2.2 A resolution.~~ The ~~cell-cycle arrest agent rapamycin binds FK506-binding protein (FKBP12) and the FKBP12-rapamycin binding (FRB) domain of FKBP12-rapamycin associated protein (FRAP) simultaneously~~, ~~and~~ the ~~inhibition of FRAP is responsible for rapamycin's biological activity. The conformation of rapamycin in the ternary complex is very similar~~ to ~~that observed in~~ the ~~FKBP12-rapamycin binary complex, with an r~~.m.~~s. difference of only 0.30 A. However, a slight (9 degrees~~ ) rotation repositions the FRB-binding face of rapamycin in the ternary complex. There are extensive rapamycin-protein interactions and relatively few interactions between the two protein partners FKBP12 and FRB, ~~these interactions mainly involving residues in~~ the ~~40s and 80s loops of FKBP12 and alpha1 and alpha4 of FRB~~. ~~The high~~-~~resolution refinement has revealed the crucial role of several buried waters in the formation of the ternary complex.~~	+	The line below this paragraph, {{ABSTRACT_PUBMED_10089303}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 10089303 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_10089303}}

	==About this Structure==		==About this Structure==
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	[[Category: Gene therapy]]		[[Category: Gene therapy]]
	[[Category: Rapamycin]]		[[Category: Rapamycin]]
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sun May~~ ~~4 22~~:23:46 2008''	+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jul 3 13:36:39 2008''

OCA at 19:23, 4 May 2008

2008-05-04T19:23:48Z

←Older revision		Revision as of 19:23, 4 May 2008
Line 1:		Line 1:
	[[Image:4fap.gif\|left\|200px]]		[[Image:4fap.gif\|left\|200px]]

-	~~{{Structure~~	+	<!--
-	~~\|PDB= 4fap \|SIZE=350\|CAPTION=~~ <~~scene name='initialview01'>4fap</scene>, resolution 2.80Å~~	+	The line below this paragraph, containing "STRUCTURE_4fap", creates the "Structure Box" on the page.
-	~~\|SITE=~~	+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	~~\|LIGAND= <scene name='pdbligand=ARD:C15~~-~~(R)~~-~~METHYLTHIENYL+RAPAMYCIN'>ARD</scene>~~	+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	~~\|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase]~~, ~~with EC number [http://www~~.~~brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </span>~~	+	or leave the SCENE parameter empty for the default display.
-	~~\|GENE= HUMAN HIPPOCAMPAL CDNA LIBRARY SOURCE 8~~ (~~CLONTECH, PALO ALTO, CA~~) (~~[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]~~)	+	-->
-	~~\|DOMAIN=~~	+	{{STRUCTURE_4fap\| PDB=4fap \| SCENE= }}
-	~~\|RELATEDENTRY=[[2fap\|2FAP]]~~, ~~[[3fap\|3FAP]]~~	+
-	~~\|RESOURCES=<span class='plainlinks'>[http://oca~~.~~weizmann.ac.il/oca~~-~~docs/fgij/fg.htm?mol=4fap FirstGlance], [http://oca.weizmann.ac.il/oca~~-~~bin/ocaids?id~~=4fap ~~OCA], [http://www.ebi.ac.uk/pdbsum/4fap PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId~~=~~4fap RCSB]</span>~~	+
-	}}	+

	'''ATOMIC STRUCTURES OF THE RAPAMYCIN ANALOGS IN COMPLEX WITH BOTH HUMAN FKBP12 AND FRB DOMAIN OF FRAP'''		'''ATOMIC STRUCTURES OF THE RAPAMYCIN ANALOGS IN COMPLEX WITH BOTH HUMAN FKBP12 AND FRB DOMAIN OF FRAP'''
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	[[Category: Clardy, J.]]		[[Category: Clardy, J.]]
	[[Category: Liang, J.]]		[[Category: Liang, J.]]
-	[[Category: ~~complex~~]]	+	[[Category: Complex]]
-	[[Category: ~~fkbp12~~]]	+	[[Category: Fkbp12]]
-	[[Category: ~~frap~~]]	+	[[Category: Frap]]
-	[[Category: ~~gene~~ therapy]]	+	[[Category: Gene therapy]]
-	[[Category: ~~rapamycin~~]]	+	[[Category: Rapamycin]]
-		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 22:23:46 2008''
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Mon Mar 31 05~~:38:39 2008''	+