4axa - Revision history

OCA at 05:49, 25 August 2022

2022-08-25T05:49:27Z

←Older revision		Revision as of 05:49, 25 August 2022
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	<StructureSection load='4axa' size='340' side='right'caption='[[4axa]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='4axa' size='340' side='right'caption='[[4axa]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4axa]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AXA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4AXA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4axa]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AXA FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RKD:(2S)-2-(4-CHLOROPHENYL)-2-HYDROXY-2-[4-(1H-PYRAZOL-4-YL)PHENYL]ETHANAMINIUM'>RKD</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RKD:(2S)-2-(4-CHLOROPHENYL)-2-HYDROXY-2-[4-(1H-PYRAZOL-4-YL)PHENYL]ETHANAMINIUM'>RKD</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='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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1cmk\|1cmk]], [[1jlu\|1jlu]], [[1kmu\|1kmu]], [[1kmw\|1kmw]], [[1q24\|1q24]], [[1q61\|1q61]], [[1q62\|1q62]], [[1q8t\|1q8t]], [[1q8u\|1q8u]], [[1q8w\|1q8w]], [[1smh\|1smh]], [[1stc\|1stc]], [[1sve\|1sve]], [[1svg\|1svg]], [[1svh\|1svh]], [[1szm\|1szm]], [[1veb\|1veb]], [[1xh4\|1xh4]], [[1xh5\|1xh5]], [[1xh6\|1xh6]], [[1xh7\|1xh7]], [[1xh8\|1xh8]], [[1xh9\|1xh9]], [[1xha\|1xha]], [[1ydr\|1ydr]], [[1yds\|1yds]], [[1ydt\|1ydt]], [[2c1a\|2c1a]], [[2c1b\|2c1b]], [[2f7e\|2f7e]], [[2gfc\|2gfc]], [[2gnf\|2gnf]], [[2gng\|2gng]], [[2gnh\|2gnh]], [[2gni\|2gni]], [[2gnj\|2gnj]], [[2gnl\|2gnl]], [[2jds\|2jds]], [[2jdt\|2jdt]], [[2jdv\|2jdv]], [[2uvx\|2uvx]], [[2uvy\|2uvy]], [[2uvz\|2uvz]], [[2uw0\|2uw0]], [[2uw3\|2uw3]], [[2uw4\|2uw4]], [[2uw5\|2uw5]], [[2uw6\|2uw6]], [[2uw7\|2uw7]], [[2uw8\|2uw8]], [[2uzt\|2uzt]], [[2uzu\|2uzu]], [[2uzv\|2uzv]], [[2uzw\|2uzw]], [[2vnw\|2vnw]], [[2vny\|2vny]], [[2vo0\|2vo0]], [[2vo3\|2vo3]], [[2vo6\|2vo6]], [[2vo7\|2vo7]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1cmk\|1cmk]], [[1jlu\|1jlu]], [[1kmu\|1kmu]], [[1kmw\|1kmw]], [[1q24\|1q24]], [[1q61\|1q61]], [[1q62\|1q62]], [[1q8t\|1q8t]], [[1q8u\|1q8u]], [[1q8w\|1q8w]], [[1smh\|1smh]], [[1stc\|1stc]], [[1sve\|1sve]], [[1svg\|1svg]], [[1svh\|1svh]], [[1szm\|1szm]], [[1veb\|1veb]], [[1xh4\|1xh4]], [[1xh5\|1xh5]], [[1xh6\|1xh6]], [[1xh7\|1xh7]], [[1xh8\|1xh8]], [[1xh9\|1xh9]], [[1xha\|1xha]], [[1ydr\|1ydr]], [[1yds\|1yds]], [[1ydt\|1ydt]], [[2c1a\|2c1a]], [[2c1b\|2c1b]], [[2f7e\|2f7e]], [[2gfc\|2gfc]], [[2gnf\|2gnf]], [[2gng\|2gng]], [[2gnh\|2gnh]], [[2gni\|2gni]], [[2gnj\|2gnj]], [[2gnl\|2gnl]], [[2jds\|2jds]], [[2jdt\|2jdt]], [[2jdv\|2jdv]], [[2uvx\|2uvx]], [[2uvy\|2uvy]], [[2uvz\|2uvz]], [[2uw0\|2uw0]], [[2uw3\|2uw3]], [[2uw4\|2uw4]], [[2uw5\|2uw5]], [[2uw6\|2uw6]], [[2uw7\|2uw7]], [[2uw8\|2uw8]], [[2uzt\|2uzt]], [[2uzu\|2uzu]], [[2uzv\|2uzv]], [[2uzw\|2uzw]], [[2vnw\|2vnw]], [[2vny\|2vny]], [[2vo0\|2vo0]], [[2vo3\|2vo3]], [[2vo6\|2vo6]], [[2vo7\|2vo7]]</div></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'>[https://en.wikipedia.org/wiki/cAMP-dependent_protein_kinase cAMP-dependent protein kinase], with EC number [https://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=4axa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4axa OCA], [~~http~~://pdbe.org/4axa PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4axa RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4axa PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4axa 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=4axa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4axa OCA], [https://pdbe.org/4axa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4axa RCSB], [https://www.ebi.ac.uk/pdbsum/4axa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4axa ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/KAPCA_BOVIN KAPCA_BOVIN]] 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) (By similarity). [[~~http~~://www.uniprot.org/uniprot/IPKA_HUMAN IPKA_HUMAN]] Extremely potent competitive inhibitor of cAMP-dependent protein kinase activity, this protein interacts with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains.	+	[[https://www.uniprot.org/uniprot/KAPCA_BOVIN KAPCA_BOVIN]] 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) (By similarity). [[https://www.uniprot.org/uniprot/IPKA_HUMAN IPKA_HUMAN]] Extremely potent competitive inhibitor of cAMP-dependent protein kinase activity, this protein interacts with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==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/>
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	</StructureSection>		</StructureSection>
	[[Category: Bovin]]		[[Category: Bovin]]
		+	[[Category: Large Structures]]
	[[Category: CAMP-dependent protein kinase]]		[[Category: CAMP-dependent protein kinase]]
	[[Category: Davies, T G]]		[[Category: Davies, T G]]

OCA at 08:48, 6 March 2019

2019-03-06T08:48:38Z

←Older revision		Revision as of 08:48, 6 March 2019
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	==Structure of PKA-PKB chimera complexed with (1S)-2-amino-1-(4- chlorophenyl)-1-(4-(1H-pyrazol-4-yl)phenyl)ethan-1-ol==		==Structure of PKA-PKB chimera complexed with (1S)-2-amino-1-(4- chlorophenyl)-1-(4-(1H-pyrazol-4-yl)phenyl)ethan-1-ol==
-	<StructureSection load='4axa' size='340' side='right' caption='[[4axa]], [[Resolution\|resolution]] 1.90Å' scene=''>	+	<StructureSection load='4axa' size='340' side='right'caption='[[4axa]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4axa]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AXA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AXA FirstGlance]. <br>		<table><tr><td colspan='2'>[[4axa]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AXA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AXA FirstGlance]. <br>

OCA at 07:24, 4 August 2016

2016-08-04T07:24:01Z

←Older revision		Revision as of 07:24, 4 August 2016
Line 1:		Line 1:
		+
	==Structure of PKA-PKB chimera complexed with (1S)-2-amino-1-(4- chlorophenyl)-1-(4-(1H-pyrazol-4-yl)phenyl)ethan-1-ol==		==Structure of PKA-PKB chimera complexed with (1S)-2-amino-1-(4- chlorophenyl)-1-(4-(1H-pyrazol-4-yl)phenyl)ethan-1-ol==
	<StructureSection load='4axa' size='340' side='right' caption='[[4axa]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='4axa' size='340' side='right' caption='[[4axa]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4axa]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Bos_taurus Bos taurus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AXA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AXA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4axa]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AXA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AXA FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RKD:(2S)-2-(4-CHLOROPHENYL)-2-HYDROXY-2-[4-(1H-PYRAZOL-4-YL)PHENYL]ETHANAMINIUM'>RKD</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RKD:(2S)-2-(4-CHLOROPHENYL)-2-HYDROXY-2-[4-(1H-PYRAZOL-4-YL)PHENYL]ETHANAMINIUM'>RKD</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='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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1cmk\|1cmk]], [[1jlu\|1jlu]], [[1kmu\|1kmu]], [[1kmw\|1kmw]], [[1q24\|1q24]], [[1q61\|1q61]], [[1q62\|1q62]], [[1q8t\|1q8t]], [[1q8u\|1q8u]], [[1q8w\|1q8w]], [[1smh\|1smh]], [[1stc\|1stc]], [[1sve\|1sve]], [[1svg\|1svg]], [[1svh\|1svh]], [[1szm\|1szm]], [[1veb\|1veb]], [[1xh4\|1xh4]], [[1xh5\|1xh5]], [[1xh6\|1xh6]], [[1xh7\|1xh7]], [[1xh8\|1xh8]], [[1xh9\|1xh9]], [[1xha\|1xha]], [[1ydr\|1ydr]], [[1yds\|1yds]], [[1ydt\|1ydt]], [[2c1a\|2c1a]], [[2c1b\|2c1b]], [[2f7e\|2f7e]], [[2gfc\|2gfc]], [[2gnf\|2gnf]], [[2gng\|2gng]], [[2gnh\|2gnh]], [[2gni\|2gni]], [[2gnj\|2gnj]], [[2gnl\|2gnl]], [[2jds\|2jds]], [[2jdt\|2jdt]], [[2jdv\|2jdv]], [[2uvx\|2uvx]], [[2uvy\|2uvy]], [[2uvz\|2uvz]], [[2uw0\|2uw0]], [[2uw3\|2uw3]], [[2uw4\|2uw4]], [[2uw5\|2uw5]], [[2uw6\|2uw6]], [[2uw7\|2uw7]], [[2uw8\|2uw8]], [[2uzt\|2uzt]], [[2uzu\|2uzu]], [[2uzv\|2uzv]], [[2uzw\|2uzw]], [[2vnw\|2vnw]], [[2vny\|2vny]], [[2vo0\|2vo0]], [[2vo3\|2vo3]], [[2vo6\|2vo6]], [[2vo7\|2vo7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1cmk\|1cmk]], [[1jlu\|1jlu]], [[1kmu\|1kmu]], [[1kmw\|1kmw]], [[1q24\|1q24]], [[1q61\|1q61]], [[1q62\|1q62]], [[1q8t\|1q8t]], [[1q8u\|1q8u]], [[1q8w\|1q8w]], [[1smh\|1smh]], [[1stc\|1stc]], [[1sve\|1sve]], [[1svg\|1svg]], [[1svh\|1svh]], [[1szm\|1szm]], [[1veb\|1veb]], [[1xh4\|1xh4]], [[1xh5\|1xh5]], [[1xh6\|1xh6]], [[1xh7\|1xh7]], [[1xh8\|1xh8]], [[1xh9\|1xh9]], [[1xha\|1xha]], [[1ydr\|1ydr]], [[1yds\|1yds]], [[1ydt\|1ydt]], [[2c1a\|2c1a]], [[2c1b\|2c1b]], [[2f7e\|2f7e]], [[2gfc\|2gfc]], [[2gnf\|2gnf]], [[2gng\|2gng]], [[2gnh\|2gnh]], [[2gni\|2gni]], [[2gnj\|2gnj]], [[2gnl\|2gnl]], [[2jds\|2jds]], [[2jdt\|2jdt]], [[2jdv\|2jdv]], [[2uvx\|2uvx]], [[2uvy\|2uvy]], [[2uvz\|2uvz]], [[2uw0\|2uw0]], [[2uw3\|2uw3]], [[2uw4\|2uw4]], [[2uw5\|2uw5]], [[2uw6\|2uw6]], [[2uw7\|2uw7]], [[2uw8\|2uw8]], [[2uzt\|2uzt]], [[2uzu\|2uzu]], [[2uzv\|2uzv]], [[2uzw\|2uzw]], [[2vnw\|2vnw]], [[2vny\|2vny]], [[2vo0\|2vo0]], [[2vo3\|2vo3]], [[2vo6\|2vo6]], [[2vo7\|2vo7]]</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=4axa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4axa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4axa RCSB], [http://www.ebi.ac.uk/pdbsum/4axa 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=4axa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4axa OCA], [http://pdbe.org/4axa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4axa RCSB], [http://www.ebi.ac.uk/pdbsum/4axa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4axa ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	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 4axa" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bos taurus~~]]	+	[[Category: Bovin]]
	[[Category: CAMP-dependent protein kinase]]		[[Category: CAMP-dependent protein kinase]]
	[[Category: Davies, T G]]		[[Category: Davies, T G]]

OCA at 06:53, 25 December 2014

2014-12-25T06:53:27Z

←Older revision		Revision as of 06:53, 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=4axa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4axa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4axa RCSB], [http://www.ebi.ac.uk/pdbsum/4axa 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=4axa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4axa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4axa RCSB], [http://www.ebi.ac.uk/pdbsum/4axa PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/KAPCA_BOVIN KAPCA_BOVIN]] 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) (By similarity). [[http://www.uniprot.org/uniprot/IPKA_HUMAN IPKA_HUMAN]] Extremely potent competitive inhibitor of cAMP-dependent protein kinase activity, this protein interacts with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 14:31, 9 December 2014

2014-12-09T14:31:59Z

←Older revision		Revision as of 14:31, 9 December 2014
Line 1:		Line 1:
-	[[~~Image:~~4axa.~~png~~\|~~left~~\|~~200px~~]]	+	==Structure of PKA-PKB chimera complexed with (1S)-2-amino-1-(4- chlorophenyl)-1-(4-(1H-pyrazol-4-yl)phenyl)ethan-1-ol==
		+	<StructureSection load='4axa' size='340' side='right' caption='[[4axa]], [[Resolution\|resolution]] 1.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4axa]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AXA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AXA FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RKD:(2S)-2-(4-CHLOROPHENYL)-2-HYDROXY-2-[4-(1H-PYRAZOL-4-YL)PHENYL]ETHANAMINIUM'>RKD</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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1cmk\|1cmk]], [[1jlu\|1jlu]], [[1kmu\|1kmu]], [[1kmw\|1kmw]], [[1q24\|1q24]], [[1q61\|1q61]], [[1q62\|1q62]], [[1q8t\|1q8t]], [[1q8u\|1q8u]], [[1q8w\|1q8w]], [[1smh\|1smh]], [[1stc\|1stc]], [[1sve\|1sve]], [[1svg\|1svg]], [[1svh\|1svh]], [[1szm\|1szm]], [[1veb\|1veb]], [[1xh4\|1xh4]], [[1xh5\|1xh5]], [[1xh6\|1xh6]], [[1xh7\|1xh7]], [[1xh8\|1xh8]], [[1xh9\|1xh9]], [[1xha\|1xha]], [[1ydr\|1ydr]], [[1yds\|1yds]], [[1ydt\|1ydt]], [[2c1a\|2c1a]], [[2c1b\|2c1b]], [[2f7e\|2f7e]], [[2gfc\|2gfc]], [[2gnf\|2gnf]], [[2gng\|2gng]], [[2gnh\|2gnh]], [[2gni\|2gni]], [[2gnj\|2gnj]], [[2gnl\|2gnl]], [[2jds\|2jds]], [[2jdt\|2jdt]], [[2jdv\|2jdv]], [[2uvx\|2uvx]], [[2uvy\|2uvy]], [[2uvz\|2uvz]], [[2uw0\|2uw0]], [[2uw3\|2uw3]], [[2uw4\|2uw4]], [[2uw5\|2uw5]], [[2uw6\|2uw6]], [[2uw7\|2uw7]], [[2uw8\|2uw8]], [[2uzt\|2uzt]], [[2uzu\|2uzu]], [[2uzv\|2uzv]], [[2uzw\|2uzw]], [[2vnw\|2vnw]], [[2vny\|2vny]], [[2vo0\|2vo0]], [[2vo3\|2vo3]], [[2vo6\|2vo6]], [[2vo7\|2vo7]]</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=4axa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4axa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4axa RCSB], [http://www.ebi.ac.uk/pdbsum/4axa PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	PURPOSE: Deregulated phosphatidylinositol 3-kinase pathway signaling through AGC kinases including AKT, p70S6 kinase, PKA, SGK and Rho kinase is a key driver of multiple cancers. The simultaneous inhibition of multiple AGC kinases may increase antitumor activity and minimize clinical resistance compared with a single pathway component. EXPERIMENTAL DESIGN: We investigated the detailed pharmacology and antitumor activity of the novel clinical drug candidate AT13148, an oral ATP-competitive multi-AGC kinase inhibitor. Gene expression microarray studies were undertaken to characterize the molecular mechanisms of action of AT13148. RESULTS: AT13148 caused substantial blockade of AKT, p70S6K, PKA, ROCK, and SGK substrate phosphorylation and induced apoptosis in a concentration and time-dependent manner in cancer cells with clinically relevant genetic defects in vitro and in vivo. Antitumor efficacy in HER2-positive, PIK3CA-mutant BT474 breast, PTEN-deficient PC3 human prostate cancer, and PTEN-deficient MES-SA uterine tumor xenografts was shown. We show for the first time that induction of AKT phosphorylation at serine 473 by AT13148, as reported for other ATP-competitive inhibitors of AKT, is not a therapeutically relevant reactivation step. Gene expression studies showed that AT13148 has a predominant effect on apoptosis genes, whereas the selective AKT inhibitor CCT128930 modulates cell-cycle genes. Induction of upstream regulators including IRS2 and PIK3IP1 as a result of compensatory feedback loops was observed. CONCLUSIONS: The clinical candidate AT13148 is a novel oral multi-AGC kinase inhibitor with potent pharmacodynamic and antitumor activity, which shows a distinct mechanism of action from other AKT inhibitors. AT13148 will now be assessed in a first-in-human phase I trial. Clin Cancer Res; 18(14); 3912-23. (c)2012 AACR.

-	~~{{STRUCTURE_4axa\| PDB=4axa \| SCENE= }}~~	+	AT13148 Is a Novel, Oral Multi-AGC Kinase Inhibitor with Potent Pharmacodynamic and Antitumor Activity.,Yap TA, Walton MI, Grimshaw KM, Te Poele RH, Eve PD, Valenti MR, de Haven Brandon AK, Martins V, Zetterlund A, Heaton SP, Heinzmann K, Jones PS, Feltell RE, Reule M, Woodhead SJ, Davies TG, Lyons JF, Raynaud FI, Eccles SA, Workman P, Thompson NT, Garrett MD Clin Cancer Res. 2012 Jul 15;18(14):3912-23. Epub 2012 Jul 10. PMID:22781553<ref>PMID:22781553</ref>

-	~~===Structure~~ of ~~PKA-PKB chimera complexed with (1S)-2-amino-1-(4- chlorophenyl)-1-(4-(1H-pyrazol-4-yl)phenyl)ethan-1-ol===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-	~~{{ABSTRACT_PUBMED_22781553}}~~	+	==See Also==
-		+	*[[CAMP-dependent protein kinase\|CAMP-dependent protein kinase]]
-	==~~About this Structure~~==	+	== References ==
-	[[~~4axa~~]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AXA OCA].	+	<references/>
-		+	__TOC__
-	==~~Reference~~==	+	</StructureSection>
-	<~~ref group="xtra">PMID:022781553<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Bos taurus]]		[[Category: Bos taurus]]
	[[Category: CAMP-dependent protein kinase]]		[[Category: CAMP-dependent protein kinase]]
-	[[Category: Davies, T G.]]	+	[[Category: Davies, T G]]
-	[[Category: Eccles, S A.]]	+	[[Category: Eccles, S A]]
-	[[Category: Eve, P D.]]	+	[[Category: Eve, P D]]
-	[[Category: Feltell, R E.]]	+	[[Category: Feltell, R E]]
-	[[Category: Garrett, M D.]]	+	[[Category: Garrett, M D]]
-	[[Category: Grimshaw, K M.]]	+	[[Category: Grimshaw, K M]]
-	[[Category: Heaton, S P.]]	+	[[Category: Heaton, S P]]
-	[[Category: Heinzmann, K.]]	+	[[Category: Heinzmann, K]]
-	[[Category: Jones, P S.]]	+	[[Category: Jones, P S]]
-	[[Category: Lyons, J F.]]	+	[[Category: Lyons, J F]]
-	[[Category: Martins, V.]]	+	[[Category: Martins, V]]
-	[[Category: Raynaud, F I.]]	+	[[Category: Raynaud, F I]]
-	[[Category: Reule, M.]]	+	[[Category: Reule, M]]
-	[[Category: Thompson, N T.]]	+	[[Category: Thompson, N T]]
-	[[Category: Valenti, M R.]]	+	[[Category: Valenti, M R]]
-	[[Category: Walton, M I.]]	+	[[Category: Walton, M I]]
-	[[Category: Woodhead, S J.]]	+	[[Category: Woodhead, S J]]
-	[[Category: Workman, P.]]	+	[[Category: Workman, P]]
-	[[Category: Yap, T A.]]	+	[[Category: Yap, T A]]
-	[[Category: Zetterlund, A.]]	+	[[Category: Zetterlund, A]]
-	[[Category: DeHavenBrandon, A K.]]	+	[[Category: DeHavenBrandon, A K]]
-	[[Category: TePoele, R H.]]	+	[[Category: TePoele, R H]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 13:11, 6 February 2013

2013-02-06T13:11:39Z

←Older revision		Revision as of 13:11, 6 February 2013
Line 1:		Line 1:
-	[[Image:4axa.~~jpg~~\|left\|200px]]	+	[[Image:4axa.png\|left\|200px]]

	{{STRUCTURE_4axa\| PDB=4axa \| SCENE= }}		{{STRUCTURE_4axa\| PDB=4axa \| SCENE= }}
Line 15:		Line 15:
	[[Category: CAMP-dependent protein kinase]]		[[Category: CAMP-dependent protein kinase]]
	[[Category: Davies, T G.]]		[[Category: Davies, T G.]]
-	[[Category: Dehavenbrandon, A K.]]
	[[Category: Eccles, S A.]]		[[Category: Eccles, S A.]]
	[[Category: Eve, P D.]]		[[Category: Eve, P D.]]
Line 28:		Line 27:
	[[Category: Raynaud, F I.]]		[[Category: Raynaud, F I.]]
	[[Category: Reule, M.]]		[[Category: Reule, M.]]
-	[[Category: Tepoele, R H.]]
	[[Category: Thompson, N T.]]		[[Category: Thompson, N T.]]
	[[Category: Valenti, M R.]]		[[Category: Valenti, M R.]]
Line 36:		Line 34:
	[[Category: Yap, T A.]]		[[Category: Yap, T A.]]
	[[Category: Zetterlund, A.]]		[[Category: Zetterlund, A.]]
		+	[[Category: DeHavenBrandon, A K.]]
		+	[[Category: TePoele, R H.]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 07:10, 25 July 2012

2012-07-25T07:10:00Z

←Older revision		Revision as of 07:10, 25 July 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4axa.jpg\|left\|200px]]

-	~~The entry~~ 4axa ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4axa\| PDB=4axa \| SCENE= }}

-	Authors: Davies, T.G., Yap, T.A., Walton, M.I., Grimshaw, K.M., tePoele, R.H., Eve, P.D., Valenti, M.R., deHavenBrandon, A.K., Martins, V., Zetterlund, A., Heaton, S.P., Heinzmann, K., Jones, P.S., Feltell, R.E., Reule, M., Woodhead, S.J., Lyons, J.F., Raynaud, F.I., Eccles, S.A., Workman, P., Thompson, N.T., Garrett, M.D.	+	===Structure of PKA-PKB chimera complexed with (1S)-2-amino-1-(4- chlorophenyl)-1-(4-(1H-pyrazol-4-yl)phenyl)ethan-1-ol===

-	~~Description:~~ Structure ~~of PKA-PKB chimera complexed~~ with ~~(1S)~~-2-~~amino-1-(4-chlorophenyl)-1-(4-(1H-pyrazol-4-yl)phenyl)ethan-1~~-ol	+	{{ABSTRACT_PUBMED_22781553}}
		+
		+	==About this Structure==
		+	[[4axa]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AXA OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022781553</ref><references group="xtra"/>
		+	[[Category: Bos taurus]]
		+	[[Category: CAMP-dependent protein kinase]]
		+	[[Category: Davies, T G.]]
		+	[[Category: Dehavenbrandon, A K.]]
		+	[[Category: Eccles, S A.]]
		+	[[Category: Eve, P D.]]
		+	[[Category: Feltell, R E.]]
		+	[[Category: Garrett, M D.]]
		+	[[Category: Grimshaw, K M.]]
		+	[[Category: Heaton, S P.]]
		+	[[Category: Heinzmann, K.]]
		+	[[Category: Jones, P S.]]
		+	[[Category: Lyons, J F.]]
		+	[[Category: Martins, V.]]
		+	[[Category: Raynaud, F I.]]
		+	[[Category: Reule, M.]]
		+	[[Category: Tepoele, R H.]]
		+	[[Category: Thompson, N T.]]
		+	[[Category: Valenti, M R.]]
		+	[[Category: Walton, M I.]]
		+	[[Category: Woodhead, S J.]]
		+	[[Category: Workman, P.]]
		+	[[Category: Yap, T A.]]
		+	[[Category: Zetterlund, A.]]
		+	[[Category: Transferase-transferase inhibitor complex]]

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

2012-06-20T07:16:51Z

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

←Older revision

Revision as of 07:16, 20 June 2012

OCA: New page: '''Unreleased structure''' The entry 4axa is ON HOLD until Paper Publication Authors: Davies, T.G., Yap, T.A., Walton, M.I., Grimshaw, K.M., tePoele, R.H., Eve, P.D., Valenti, M.R., deH...

2012-06-20T07:16:50Z

New page: '''Unreleased structure''' The entry 4axa is ON HOLD until Paper Publication Authors: Davies, T.G., Yap, T.A., Walton, M.I., Grimshaw, K.M., tePoele, R.H., Eve, P.D., Valenti, M.R., deH...

New page

'''Unreleased structure'''

The entry 4axa is ON HOLD until Paper Publication

Authors: Davies, T.G., Yap, T.A., Walton, M.I., Grimshaw, K.M., tePoele, R.H., Eve, P.D., Valenti, M.R., deHavenBrandon, A.K., Martins, V., Zetterlund, A., Heaton, S.P., Heinzmann, K., Jones, P.S., Feltell, R.E., Reule, M., Woodhead, S.J., Lyons, J.F., Raynaud, F.I., Eccles, S.A., Workman, P., Thompson, N.T., Garrett, M.D.

Description: Structure of PKA-PKB chimera complexed with (1S)-2-amino-1-(4-chlorophenyl)-1-(4-(1H-pyrazol-4-yl)phenyl)ethan-1-ol