4xx9 - Revision history

OCA at 07:51, 27 September 2023

OCA — Wed, 27 Sep 2023 07:51:41 GMT

←Older revision		Revision as of 07:51, 27 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4xx9]] 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=4XX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XX9 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4xx9]] 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=4XX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XX9 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RF4:(2-{[2-(2,6-DIMETHYLPHENOXY)ETHYL]SULFANYL}-1H-BENZIMIDAZOL-1-YL)ACETIC+ACID'>RF4</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RF4:(2-{[2-(2,6-DIMETHYLPHENOXY)ETHYL]SULFANYL}-1H-BENZIMIDAZOL-1-YL)ACETIC+ACID'>RF4</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4xx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xx9 OCA], [https://pdbe.org/4xx9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xx9 RCSB], [https://www.ebi.ac.uk/pdbsum/4xx9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xx9 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=4xx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xx9 OCA], [https://pdbe.org/4xx9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xx9 RCSB], [https://www.ebi.ac.uk/pdbsum/4xx9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xx9 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 17:56, 26 April 2023

OCA — Wed, 26 Apr 2023 17:56:32 GMT

←Older revision		Revision as of 17:56, 26 April 2023
Line 3:		Line 3:
	<StructureSection load='4xx9' size='340' side='right'caption='[[4xx9]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='4xx9' size='340' side='right'caption='[[4xx9]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4xx9]] 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=4XX9 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4XX9 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4xx9]] 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=4XX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XX9 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RF4:(2-{[2-(2,6-DIMETHYLPHENOXY)ETHYL]SULFANYL}-1H-BENZIMIDAZOL-1-YL)ACETIC+ACID'>RF4</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RF4:(2-{[2-(2,6-DIMETHYLPHENOXY)ETHYL]SULFANYL}-1H-BENZIMIDAZOL-1-YL)ACETIC+ACID'>RF4</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene~~></td></tr>~~	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4xx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xx9 OCA], [https://pdbe.org/4xx9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xx9 RCSB], [https://www.ebi.ac.uk/pdbsum/4xx9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xx9 ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDPK1, PDK1 ([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='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=4xx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xx9 OCA], [~~http~~://pdbe.org/4xx9 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4xx9 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4xx9 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4xx9 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PDPK1_HUMAN PDPK1_HUMAN]] Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages. Isoform 3 is catalytically inactive.<ref>PMID:9094314</ref> <ref>PMID:9768361</ref> <ref>PMID:9707564</ref> <ref>PMID:9445476</ref> <ref>PMID:10480933</ref> <ref>PMID:10995762</ref> <ref>PMID:12167717</ref> <ref>PMID:14585963</ref> <ref>PMID:14604990</ref> <ref>PMID:10226025</ref> <ref>PMID:16207722</ref> <ref>PMID:16251192</ref> <ref>PMID:17327236</ref> <ref>PMID:17371830</ref> <ref>PMID:18835241</ref>	+	[https://www.uniprot.org/uniprot/PDPK1_HUMAN PDPK1_HUMAN] Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages. Isoform 3 is catalytically inactive.<ref>PMID:9094314</ref> <ref>PMID:9768361</ref> <ref>PMID:9707564</ref> <ref>PMID:9445476</ref> <ref>PMID:10480933</ref> <ref>PMID:10995762</ref> <ref>PMID:12167717</ref> <ref>PMID:14585963</ref> <ref>PMID:14604990</ref> <ref>PMID:10226025</ref> <ref>PMID:16207722</ref> <ref>PMID:16251192</ref> <ref>PMID:17327236</ref> <ref>PMID:17371830</ref> <ref>PMID:18835241</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Rettenmaier TJ]]
-	[[Category: Rettenmaier~~, T J~~]]	+	[[Category: Wells JA]]
-	[[Category: Wells~~, J A]]~~	+
-	~~[[Category: Allostery]]~~	+
-	~~[[Category: Protein kinase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 23:29, 5 June 2019

OCA — Wed, 05 Jun 2019 23:29:04 GMT

←Older revision		Revision as of 23:29, 5 June 2019
Line 1:		Line 1:
		+
	==Crystal structure of PDK1 in complex with ATP and the PIF-pocket ligand RF4==		==Crystal structure of PDK1 in complex with ATP and the PIF-pocket ligand RF4==
-	<StructureSection load='4xx9' size='340' side='right' caption='[[4xx9]], [[Resolution\|resolution]] 1.40Å' scene=''>	+	<StructureSection load='4xx9' size='340' side='right'caption='[[4xx9]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4xx9]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XX9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XX9 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4xx9]] 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=4XX9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XX9 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RF4:(2-{[2-(2,6-DIMETHYLPHENOXY)ETHYL]SULFANYL}-1H-BENZIMIDAZOL-1-YL)ACETIC+ACID'>RF4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RF4:(2-{[2-(2,6-DIMETHYLPHENOXY)ETHYL]SULFANYL}-1H-BENZIMIDAZOL-1-YL)ACETIC+ACID'>RF4</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDPK1, PDK1 ([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=4xx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xx9 OCA], [http://pdbe.org/4xx9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xx9 RCSB], [http://www.ebi.ac.uk/pdbsum/4xx9 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=4xx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xx9 OCA], [http://pdbe.org/4xx9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xx9 RCSB], [http://www.ebi.ac.uk/pdbsum/4xx9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xx9 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 4xx9" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4xx9" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Pdk1 3D structures\|Pdk1 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Rettenmaier, T J]]		[[Category: Rettenmaier, T J]]

OCA at 05:24, 22 October 2015

OCA — Thu, 22 Oct 2015 05:24:00 GMT

←Older revision		Revision as of 05:24, 22 October 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Crystal structure of PDK1 in complex with ATP and the PIF-pocket ligand RF4==
		+	<StructureSection load='4xx9' size='340' side='right' caption='[[4xx9]], [[Resolution\|resolution]] 1.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4xx9]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XX9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XX9 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RF4:(2-{[2-(2,6-DIMETHYLPHENOXY)ETHYL]SULFANYL}-1H-BENZIMIDAZOL-1-YL)ACETIC+ACID'>RF4</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=4xx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xx9 OCA], [http://pdbe.org/4xx9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xx9 RCSB], [http://www.ebi.ac.uk/pdbsum/4xx9 PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PDPK1_HUMAN PDPK1_HUMAN]] Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages. Isoform 3 is catalytically inactive.<ref>PMID:9094314</ref> <ref>PMID:9768361</ref> <ref>PMID:9707564</ref> <ref>PMID:9445476</ref> <ref>PMID:10480933</ref> <ref>PMID:10995762</ref> <ref>PMID:12167717</ref> <ref>PMID:14585963</ref> <ref>PMID:14604990</ref> <ref>PMID:10226025</ref> <ref>PMID:16207722</ref> <ref>PMID:16251192</ref> <ref>PMID:17327236</ref> <ref>PMID:17371830</ref> <ref>PMID:18835241</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Finding small molecules that target allosteric sites remains a grand challenge for ligand discovery. In the protein kinase field, only a handful of highly selective allosteric modulators have been found. Thus, more general methods are needed to discover allosteric modulators for additional kinases. Here, we use virtual screening against an ensemble of both crystal structures and comparative models to identify ligands for an allosteric peptide-binding site on the protein kinase PDK1 (the PIF pocket). We optimized these ligands through an analog-by-catalog search that yielded compound 4, which binds to PDK1 with 8 muM affinity. We confirmed the docking poses by determining a crystal structure of PDK1 in complex with 4. Because the PIF pocket appears to be a recurring structural feature of the kinase fold, known generally as the helix alphaC patch, this approach may enable the discovery of allosteric modulators for other kinases.

-	~~The entry 4xx9 is ON HOLD until Paper Publication~~	+	Small-Molecule Allosteric Modulators of the Protein Kinase PDK1 from Structure-Based Docking.,Rettenmaier TJ, Fan H, Karpiak J, Doak A, Sali A, Shoichet BK, Wells JA J Med Chem. 2015 Oct 12. PMID:26443011<ref>PMID:26443011</ref>

-	~~Authors: Rettenmaier~~, T.J.~~, Wells, J.A~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: Crystal structure of PDK1 in complex with ATP and the PIF~~-~~pocket ligand RF4~~	+	<div class="pdbe-citations 4xx9" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Unreleased Structures~~]]	+	== References ==
-	[[Category: Rettenmaier, T.J]]	+	<references/>
-	[[Category: Wells, J.A]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Rettenmaier, T J]]
		+	[[Category: Wells, J A]]
		+	[[Category: Allostery]]
		+	[[Category: Protein kinase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

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	Authors: Rettenmaier, T.J., Wells, J.A.		Authors: Rettenmaier, T.J., Wells, J.A.

OCA: Protected "4xx9" [edit=sysop:move=sysop]

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Protected "4xx9" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:56, 7 February 2015

OCA: New page: '''Unreleased structure''' The entry 4xx9 is ON HOLD Authors: Rettenmaier, T.J., Wells, J.A. Description: Crystal structure of PDK1 in complex with ATP and the PIF-pocket ligand RF4 [[...

OCA — Sat, 07 Feb 2015 14:56:51 GMT

New page: '''Unreleased structure''' The entry 4xx9 is ON HOLD Authors: Rettenmaier, T.J., Wells, J.A. Description: Crystal structure of PDK1 in complex with ATP and the PIF-pocket ligand RF4 [[...

New page

'''Unreleased structure'''

The entry 4xx9 is ON HOLD

Authors: Rettenmaier, T.J., Wells, J.A.

Description: Crystal structure of PDK1 in complex with ATP and the PIF-pocket ligand RF4
[[Category: Unreleased Structures]]
[[Category: Rettenmaier, T.J]]
[[Category: Wells, J.A]]