4ib1 - Revision history

OCA at 08:55, 9 November 2022

2022-11-09T08:55:08Z

←Older revision		Revision as of 08:55, 9 November 2022
Line 1:		Line 1:

	==Structure of cAMP dependent protein kinase A in complex with high K+ concentration, ADP and phosphorylated peptide pSP20==		==Structure of cAMP dependent protein kinase A in complex with high K+ concentration, ADP and phosphorylated peptide pSP20==
-	<StructureSection load='4ib1' size='340' side='right' caption='[[4ib1]], [[Resolution\|resolution]] 1.63Å' scene=''>	+	<StructureSection load='4ib1' size='340' side='right'caption='[[4ib1]], [[Resolution\|resolution]] 1.63Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ib1]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Lk3_transgenic_mice Lk3 transgenic mice~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IB1 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4IB1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ib1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IB1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IB1 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=K:POTASSIUM+ION'>K</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=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=4ib1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ib1 OCA], [https://pdbe.org/4ib1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ib1 RCSB], [https://www.ebi.ac.uk/pdbsum/4ib1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ib1 ProSAT]</span></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4iac\|4iac]], [[4iad\|4iad]], [[4iaf\|4iaf]], [[4iai\|4iai]], [[4iak\|4iak]], [[4iay\|4iay]], [[4iaz\|4iaz]], [[4ib0\|4ib0]], [[4ib3\|4ib3]]</td></tr>	+
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Prkaca, Pkaca ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/cAMP-dependent_protein_kinase cAMP-dependent protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.11 2.7.11.11] </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=4ib1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ib1 OCA], [~~http~~://pdbe.org/4ib1 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ib1 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ib1 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ib1 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/KAPCA_MOUSE KAPCA_MOUSE]] Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, TRPC1 and VASP. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). TRPC1 activation by phosphorylation promotes Ca(2+) influx, essential for the increase in permeability induced by thrombin in confluent endothelial monolayers. PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Regulates negatively tight junction (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT).<ref>PMID:15340140</ref> <ref>PMID:19223768</ref> <ref>PMID:19560455</ref>	+	[https://www.uniprot.org/uniprot/KAPCA_MOUSE KAPCA_MOUSE] Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, TRPC1 and VASP. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). TRPC1 activation by phosphorylation promotes Ca(2+) influx, essential for the increase in permeability induced by thrombin in confluent endothelial monolayers. PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Regulates negatively tight junction (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT).<ref>PMID:15340140</ref> <ref>PMID:19223768</ref> <ref>PMID:19560455</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 20:

	==See Also==		==See Also==
-	*[[CAMP-dependent protein kinase\|CAMP-dependent protein kinase]]	+	*[[CAMP-dependent protein kinase 3D structures\|CAMP-dependent protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Lk3 transgenic mice~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~CAMP-dependent protein kinase~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Gerlits, O~~]]	+	[[Category: Mus musculus]]
-	[[Category: ~~Kovalevsky, A~~]]	+	[[Category: Gerlits O]]
-	[[Category: ~~Kinase enzyme]]~~	+	[[Category: Kovalevsky A]]
-	~~[[Category: Phosphorylated]]~~	+
-	~~[[Category: Phosphotransfer]]~~	+
-	~~[[Category: Transferase-peptide complex~~]]	+

OCA at 12:18, 5 August 2016

2016-08-05T12:18:44Z

←Older revision		Revision as of 12:18, 5 August 2016
Line 1:		Line 1:
		+
	==Structure of cAMP dependent protein kinase A in complex with high K+ concentration, ADP and phosphorylated peptide pSP20==		==Structure of cAMP dependent protein kinase A in complex with high K+ concentration, ADP and phosphorylated peptide pSP20==
	<StructureSection load='4ib1' size='340' side='right' caption='[[4ib1]], [[Resolution\|resolution]] 1.63Å' scene=''>		<StructureSection load='4ib1' size='340' side='right' caption='[[4ib1]], [[Resolution\|resolution]] 1.63Å' scene=''>
Line 8:		Line 9:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Prkaca, Pkaca ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Prkaca, Pkaca ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/cAMP-dependent_protein_kinase cAMP-dependent protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.11 2.7.11.11] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/cAMP-dependent_protein_kinase cAMP-dependent protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.11 2.7.11.11] </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=4ib1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ib1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ib1 RCSB], [http://www.ebi.ac.uk/pdbsum/4ib1 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=4ib1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ib1 OCA], [http://pdbe.org/4ib1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ib1 RCSB], [http://www.ebi.ac.uk/pdbsum/4ib1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ib1 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 20:		Line 21:
	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 4ib1" style="background-color:#fffaf0;"></div>

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

OCA at 18:46, 25 December 2014

2014-12-25T18:46:56Z

←Older revision		Revision as of 18:46, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ib1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IB1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IB1 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ib1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IB1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IB1 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene><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=K:POTASSIUM+ION'>K</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4iac\|4iac]], [[4iad\|4iad]], [[4iaf\|4iaf]], [[4iai\|4iai]], [[4iak\|4iak]], [[4iay\|4iay]], [[4iaz\|4iaz]], [[4ib0\|4ib0]], [[4ib3\|4ib3]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4iac\|4iac]], [[4iad\|4iad]], [[4iaf\|4iaf]], [[4iai\|4iai]], [[4iak\|4iak]], [[4iay\|4iay]], [[4iaz\|4iaz]], [[4ib0\|4ib0]], [[4ib3\|4ib3]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Prkaca, Pkaca ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Prkaca, Pkaca ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/cAMP-dependent_protein_kinase cAMP-dependent protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.11 2.7.11.11] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/cAMP-dependent_protein_kinase cAMP-dependent protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.11 2.7.11.11] </span></td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ib1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ib1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ib1 RCSB], [http://www.ebi.ac.uk/pdbsum/4ib1 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=4ib1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ib1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ib1 RCSB], [http://www.ebi.ac.uk/pdbsum/4ib1 PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/KAPCA_MOUSE KAPCA_MOUSE]] Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, TRPC1 and VASP. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). TRPC1 activation by phosphorylation promotes Ca(2+) influx, essential for the increase in permeability induced by thrombin in confluent endothelial monolayers. PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Regulates negatively tight junction (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT).<ref>PMID:15340140</ref> <ref>PMID:19223768</ref> <ref>PMID:19560455</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 16:		Line 18:
	Metal-Free cAMP-Dependent Protein Kinase Can Catalyze Phosphoryl Transfer.,Gerlits O, Das A, Keshwani MM, Taylor S, Waltman MJ, Langan P, Heller WT, Kovalevsky A Biochemistry. 2014 May 20;53(19):3179-86. doi: 10.1021/bi5000965. Epub 2014 May, 8. PMID:24786636<ref>PMID:24786636</ref>		Metal-Free cAMP-Dependent Protein Kinase Can Catalyze Phosphoryl Transfer.,Gerlits O, Das A, Keshwani MM, Taylor S, Waltman MJ, Langan P, Heller WT, Kovalevsky A Biochemistry. 2014 May 20;53(19):3179-86. doi: 10.1021/bi5000965. Epub 2014 May, 8. PMID:24786636<ref>PMID:24786636</ref>

-	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, 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>
		+
		+	==See Also==
		+	*[[CAMP-dependent protein kinase\|CAMP-dependent protein kinase]]
	== References ==		== References ==
	<references/>		<references/>
Line 24:		Line 29:
	[[Category: Lk3 transgenic mice]]		[[Category: Lk3 transgenic mice]]
	[[Category: CAMP-dependent protein kinase]]		[[Category: CAMP-dependent protein kinase]]
-	[[Category: Gerlits, O.]]	+	[[Category: Gerlits, O]]
-	[[Category: Kovalevsky, A.]]	+	[[Category: Kovalevsky, A]]
	[[Category: Kinase enzyme]]		[[Category: Kinase enzyme]]
	[[Category: Phosphorylated]]		[[Category: Phosphorylated]]
	[[Category: Phosphotransfer]]		[[Category: Phosphotransfer]]
	[[Category: Transferase-peptide complex]]		[[Category: Transferase-peptide complex]]

OCA at 07:18, 28 May 2014

2014-05-28T07:18:08Z

←Older revision		Revision as of 07:18, 28 May 2014
Line 12:		Line 12:
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	X-ray structures of several ternary ~~substrate and~~ product complexes of the catalytic subunit of cAMP-dependent protein kinase (PKAc) have been determined with ~~different~~ bound metal ions~~. In the PKAc complexes, Mg2+, Ca2+, Sr2+,~~ and ~~Ba2~~+ metal ~~ions could bind to the active site~~ and facilitate the phosphoryl transfer reaction. ATP and a substrate peptide (SP20) were modified~~, and~~ the ~~reaction~~ products ADP and the phosphorylated peptide were found ~~trapped~~ in the ~~enzyme~~ active site. ~~Finally~~, ~~we determined~~ the structure of ~~a pseudo~~-~~Michaelis~~ complex ~~containing Mg2+, nonhydrolyzable AMP~~-~~PCP (beta~~,~~gamma-methyleneadenosine 5'-triphosphate) and SP20. The product structures together~~ with the ~~pseudo-Michaelis complex provide snapshots of different stages of the phosphorylation reaction~~. Comparison of these structures reveals conformational~~, coordination,~~ and hydrogen bonding changes that might ~~occur during~~ the ~~reaction and shed new light on its~~ mechanism~~, roles~~ of ~~metals, and active site residues~~.	+	X-ray structures of several ternary product complexes of the catalytic subunit of cAMP-dependent protein kinase (PKAc) have been determined with no bound metal ions and with Na(+) or K(+) coordinated at two metal-binding sites. The metal-free PKAc and the enzyme with alkali metals were able to facilitate the phosphoryl transfer reaction. In all studied complexes, the ATP and the substrate peptide (SP20) were modified into the products ADP and the phosphorylated peptide. The products of the phosphotransfer reaction were also found when ATP-gammaS, a nonhydrolyzable ATP analogue, reacted with SP20 in the PKAc active site containing no metals. Single turnover enzyme kinetics measurements utilizing (32)P-labeled ATP confirmed the phosphotransferase activity of the enzyme in the absence of metal ions and in the presence of alkali metals. In addition, the structure of the apo-PKAc binary complex with SP20 suggests that the sequence of binding events may become ordered in a metal-free environment, with SP20 binding first to prime the enzyme for subsequent ATP binding. Comparison of these structures reveals conformational and hydrogen bonding changes that might be important for the mechanism of catalysis.

-	~~Insights into the Phosphoryl Transfer Catalyzed by~~ cAMP-Dependent Protein Kinase~~: An X-ray Crystallographic Study of Complexes with Various Metals and Peptide Substrate SP20~~.,Gerlits O, ~~Waltman MJ~~, Taylor S, Langan P, Kovalevsky A Biochemistry. ~~2013~~ May 14. PMID:~~23672593~~<ref>PMID:~~23672593~~</ref>	+	Metal-Free cAMP-Dependent Protein Kinase Can Catalyze Phosphoryl Transfer.,Gerlits O, Das A, Keshwani MM, Taylor S, Waltman MJ, Langan P, Heller WT, Kovalevsky A Biochemistry. 2014 May 20;53(19):3179-86. doi: 10.1021/bi5000965. Epub 2014 May, 8. PMID:24786636<ref>PMID:24786636</ref>

	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>		From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>

OCA at 07:05, 21 May 2014

2014-05-21T07:05:48Z

←Older revision		Revision as of 07:05, 21 May 2014
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-	~~{{STRUCTURE_4ib1\| PDB=4ib1 \| SCENE= }}~~	+	==Structure of cAMP dependent protein kinase A in complex with high K+ concentration, ADP and phosphorylated peptide pSP20==
-	===Structure of cAMP dependent protein kinase A in complex with high K+ concentration, ADP and phosphorylated peptide pSP20===	+	<StructureSection load='4ib1' size='340' side='right' caption='[[4ib1]], [[Resolution\|resolution]] 1.63Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4ib1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IB1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IB1 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4iac\|4iac]], [[4iad\|4iad]], [[4iaf\|4iaf]], [[4iai\|4iai]], [[4iak\|4iak]], [[4iay\|4iay]], [[4iaz\|4iaz]], [[4ib0\|4ib0]], [[4ib3\|4ib3]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Prkaca, Pkaca ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/cAMP-dependent_protein_kinase cAMP-dependent protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.11 2.7.11.11] </span></td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ib1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ib1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ib1 RCSB], [http://www.ebi.ac.uk/pdbsum/4ib1 PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	X-ray structures of several ternary substrate and product complexes of the catalytic subunit of cAMP-dependent protein kinase (PKAc) have been determined with different bound metal ions. In the PKAc complexes, Mg2+, Ca2+, Sr2+, and Ba2+ metal ions could bind to the active site and facilitate the phosphoryl transfer reaction. ATP and a substrate peptide (SP20) were modified, and the reaction products ADP and the phosphorylated peptide were found trapped in the enzyme active site. Finally, we determined the structure of a pseudo-Michaelis complex containing Mg2+, nonhydrolyzable AMP-PCP (beta,gamma-methyleneadenosine 5'-triphosphate) and SP20. The product structures together with the pseudo-Michaelis complex provide snapshots of different stages of the phosphorylation reaction. Comparison of these structures reveals conformational, coordination, and hydrogen bonding changes that might occur during the reaction and shed new light on its mechanism, roles of metals, and active site residues.

-	~~==Function==~~	+	Insights into the Phosphoryl Transfer Catalyzed by cAMP-Dependent Protein Kinase: An X-ray Crystallographic Study of Complexes with Various Metals and Peptide Substrate SP20.,Gerlits O, Waltman MJ, Taylor S, Langan P, Kovalevsky A Biochemistry. 2013 May 14. PMID:23672593<ref>PMID:23672593</ref>
-	~~[[http://www.uniprot.org/uniprot/KAPCA_MOUSE KAPCA_MOUSE]] Phosphorylates a large number of substrates in~~ the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, TRPC1 and VASP. RORA is activated by ~~phosphorylation. Required for glucose~~-~~mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the regulation~~ of ~~platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex~~ with ~~NF-kappa-B (NFKB1~~ and ~~NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP~~. Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, ~~despite reduced wave amplitude and resting cytosolic Ca(2+). TRPC1 activation by phosphorylation promotes Ca(2+) influx~~, essential for the increase in permeability induced by thrombin in confluent endothelial monolayers. PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Regulates negatively tight junction (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May ~~also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT)~~.~~<ref>~~PMID:~~15340140</ref> <ref>PMID:19223768</ref>~~ <ref>PMID:~~19560455~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4ib1]] is~~ a ~~2 chain structure~~. ~~Full crystallographic information is available from [http://oca~~.~~weizmann~~.~~ac.il~~/~~oca-bin/ocashort?id=4IB1 OCA].~~	+	</div>
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
		+	[[Category: Lk3 transgenic mice]]
	[[Category: CAMP-dependent protein kinase]]		[[Category: CAMP-dependent protein kinase]]
	[[Category: Gerlits, O.]]		[[Category: Gerlits, O.]]

OCA at 13:47, 11 December 2013

2013-12-11T13:47:33Z

←Older revision		Revision as of 13:47, 11 December 2013
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-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4ib1\| PDB=4ib1 \| SCENE= }}
		+	===Structure of cAMP dependent protein kinase A in complex with high K+ concentration, ADP and phosphorylated peptide pSP20===

-	~~The entry 4ib1~~ is ~~ON HOLD~~ ~~until Jan 06 2015~~	+	==Function==
		+	[[http://www.uniprot.org/uniprot/KAPCA_MOUSE KAPCA_MOUSE]] Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, TRPC1 and VASP. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). TRPC1 activation by phosphorylation promotes Ca(2+) influx, essential for the increase in permeability induced by thrombin in confluent endothelial monolayers. PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Regulates negatively tight junction (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT).<ref>PMID:15340140</ref> <ref>PMID:19223768</ref> <ref>PMID:19560455</ref>

-	~~Authors~~: ~~Gerlits, O~~.~~, Kovalevsky, A~~.	+	==About this Structure==
		+	[[4ib1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IB1 OCA].

-	~~Description~~: ~~Structure of cAMP~~ dependent protein kinase ~~A in complex with high K+ concentration~~, ~~ADP and phosphorylated~~ peptide ~~pSP20~~	+	==Reference==
		+	<references group="xtra"/><references/>
		+	[[Category: CAMP-dependent protein kinase]]
		+	[[Category: Gerlits, O.]]
		+	[[Category: Kovalevsky, A.]]
		+	[[Category: Kinase enzyme]]
		+	[[Category: Phosphorylated]]
		+	[[Category: Phosphotransfer]]
		+	[[Category: Transferase-peptide complex]]

OCA at 06:33, 4 December 2013

2013-12-04T06:33:19Z

←Older revision		Revision as of 06:33, 4 December 2013
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4ib1 is ON HOLD until ~~Paper Publication~~	+	The entry 4ib1 is ON HOLD until Jan 06 2015

	Authors: Gerlits, O., Kovalevsky, A.		Authors: Gerlits, O., Kovalevsky, A.

	Description: Structure of cAMP dependent protein kinase A in complex with high K+ concentration, ADP and phosphorylated peptide pSP20		Description: Structure of cAMP dependent protein kinase A in complex with high K+ concentration, ADP and phosphorylated peptide pSP20

OCA at 08:22, 16 January 2013

2013-01-16T08:22:59Z

←Older revision		Revision as of 08:22, 16 January 2013
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4ib1 is ON HOLD	+	The entry 4ib1 is ON HOLD until Paper Publication

	Authors: Gerlits, O., Kovalevsky, A.		Authors: Gerlits, O., Kovalevsky, A.

	Description: Structure of cAMP dependent protein kinase A in complex with high K+ concentration, ADP and phosphorylated peptide pSP20		Description: Structure of cAMP dependent protein kinase A in complex with high K+ concentration, ADP and phosphorylated peptide pSP20

OCA: Protected "4ib1" [edit=sysop:move=sysop]

2012-12-19T11:05:45Z

Protected "4ib1" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:05, 19 December 2012

OCA: New page: '''Unreleased structure''' The entry 4ib1 is ON HOLD Authors: Gerlits, O., Kovalevsky, A. Description: Structure of cAMP dependent protein kinase A in complex with high K+ concentratio...

2012-12-19T11:05:44Z

New page: '''Unreleased structure''' The entry 4ib1 is ON HOLD Authors: Gerlits, O., Kovalevsky, A. Description: Structure of cAMP dependent protein kinase A in complex with high K+ concentratio...

New page

'''Unreleased structure'''

The entry 4ib1 is ON HOLD

Authors: Gerlits, O., Kovalevsky, A.

Description: Structure of cAMP dependent protein kinase A in complex with high K+ concentration, ADP and phosphorylated peptide pSP20