1veb - Revision history

OCA at 00:02, 28 December 2023

OCA — Thu, 28 Dec 2023 00:02:29 GMT

←Older revision		Revision as of 00:02, 28 December 2023
Line 3:		Line 3:
	<StructureSection load='1veb' size='340' side='right'caption='[[1veb]], [[Resolution\|resolution]] 2.89Å' scene=''>		<StructureSection load='1veb' size='340' side='right'caption='[[1veb]], [[Resolution\|resolution]] 2.89Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1veb]] 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=1VEB OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=1VEB FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1veb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VEB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1VEB FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I05:(3R,4R)-N-{4-[4-(2-FLUORO-6-HYDROXY-3-METHOXY-BENZOYL)-BENZYLOXY]-AZEPAN-3-YL}-ISONICOTINAMIDE'>I05</scene>~~</td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.89Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I05:(3R,4R)-N-{4-[4-(2-FLUORO-6-HYDROXY-3-METHOXY-BENZOYL)-BENZYLOXY]-AZEPAN-3-YL}-ISONICOTINAMIDE'>I05</scene>, <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"><div style='overflow: auto; max-height: 3em;'>[[1sve\|1sve]], [[1svg\|1svg]], [[1svh\|1svh]]</div></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=1veb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1veb OCA], [https://pdbe.org/1veb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1veb RCSB], [https://www.ebi.ac.uk/pdbsum/1veb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1veb ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr>~~	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </span></td></tr>	+
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=1veb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1veb OCA], [~~http~~://pdbe.org/1veb PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1veb RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1veb PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1veb 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).
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bovin~~]]	+	[[Category: Bos taurus]]
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Transferase]]~~	+	[[Category: Berillon L]]
-	[[Category: Berillon, L]]	+	[[Category: Breitenlechner CB]]
-	[[Category: Breitenlechner~~, C B~~]]	+	[[Category: Engh RA]]
-	[[Category: Engh~~, R A~~]]	+	[[Category: Friebe W-G]]
-	[[Category: Friebe, W G]]	+	[[Category: Graul K]]
-	[[Category: Graul, K]]	+	[[Category: Huber R]]
-	[[Category: Huber, R]]	+	[[Category: Marzenell K]]
-	[[Category: Marzenell, K]]	+	[[Category: Masjost B]]
-	[[Category: Masjost, B]]	+	[[Category: Schumacher R]]
-	[[Category: Schumacher, R]]	+	[[Category: Thomas U]]
-	[[Category: Thomas, U]]	+	[[Category: Wegge T]]
-	[[Category: Wegge, T]]	+
-	~~[[Category: Balanol derivative]]~~	+
-	~~[[Category: Kinase-inhibitor-complex]]~~	+
-	~~[[Category: Serine/threonine-protein kinase~~]]	+

OCA at 07:35, 30 December 2020

OCA — Wed, 30 Dec 2020 07:35:24 GMT

←Older revision		Revision as of 07:35, 30 December 2020
Line 1:		Line 1:

	==Crystal Structure of Protein Kinase A in Complex with Azepane Derivative 5==		==Crystal Structure of Protein Kinase A in Complex with Azepane Derivative 5==
-	<StructureSection load='1veb' size='340' side='right' caption='[[1veb]], [[Resolution\|resolution]] 2.89Å' scene=''>	+	<StructureSection load='1veb' size='340' side='right'caption='[[1veb]], [[Resolution\|resolution]] 2.89Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1veb]] 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=1VEB OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1VEB FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1veb]] 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=1VEB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1VEB FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=I05:(3R,4R)-N-{4-[4-(2-FLUORO-6-HYDROXY-3-METHOXY-BENZOYL)-BENZYLOXY]-AZEPAN-3-YL}-ISONICOTINAMIDE'>I05</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I05:(3R,4R)-N-{4-[4-(2-FLUORO-6-HYDROXY-3-METHOXY-BENZOYL)-BENZYLOXY]-AZEPAN-3-YL}-ISONICOTINAMIDE'>I05</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">[[1sve\|1sve]], [[1svg\|1svg]], [[1svh\|1svh]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1sve\|1sve]], [[1svg\|1svg]], [[1svh\|1svh]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </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=1veb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1veb OCA], [http://pdbe.org/1veb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1veb RCSB], [http://www.ebi.ac.uk/pdbsum/1veb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1veb ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1veb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1veb OCA], [http://pdbe.org/1veb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1veb RCSB], [http://www.ebi.ac.uk/pdbsum/1veb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1veb ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 34:		Line 34:

	==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/>
Line 40:		Line 40:
	</StructureSection>		</StructureSection>
	[[Category: Bovin]]		[[Category: Bovin]]
		+	[[Category: Large Structures]]
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Berillon, L]]		[[Category: Berillon, L]]

OCA at 07:41, 4 April 2018

OCA — Wed, 04 Apr 2018 07:41:45 GMT

←Older revision		Revision as of 07:41, 4 April 2018
Line 1:		Line 1:
		+
	==Crystal Structure of Protein Kinase A in Complex with Azepane Derivative 5==		==Crystal Structure of Protein Kinase A in Complex with Azepane Derivative 5==
	<StructureSection load='1veb' size='340' side='right' caption='[[1veb]], [[Resolution\|resolution]] 2.89Å' scene=''>		<StructureSection load='1veb' size='340' side='right' caption='[[1veb]], [[Resolution\|resolution]] 2.89Å' scene=''>
Line 8:		Line 9:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </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=1veb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1veb OCA], [http://pdbe.org/1veb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1veb RCSB], [http://www.ebi.ac.uk/pdbsum/1veb 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=1veb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1veb OCA], [http://pdbe.org/1veb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1veb RCSB], [http://www.ebi.ac.uk/pdbsum/1veb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1veb ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 16:		Line 17:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ve/1veb_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ve/1veb_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>

OCA at 21:01, 9 February 2016

OCA — Tue, 09 Feb 2016 21:01:43 GMT

←Older revision		Revision as of 21:01, 9 February 2016
Line 20:		Line 20:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1veb ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 01:59, 11 September 2015

OCA — Fri, 11 Sep 2015 01:59:49 GMT

←Older revision		Revision as of 01:59, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='1veb' size='340' side='right' caption='[[1veb]], [[Resolution\|resolution]] 2.89Å' scene=''>		<StructureSection load='1veb' size='340' side='right' caption='[[1veb]], [[Resolution\|resolution]] 2.89Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1veb]] 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=1VEB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1VEB FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1veb]] 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=1VEB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1VEB FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=I05:(3R,4R)-N-{4-[4-(2-FLUORO-6-HYDROXY-3-METHOXY-BENZOYL)-BENZYLOXY]-AZEPAN-3-YL}-ISONICOTINAMIDE'>I05</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=I05:(3R,4R)-N-{4-[4-(2-FLUORO-6-HYDROXY-3-METHOXY-BENZOYL)-BENZYLOXY]-AZEPAN-3-YL}-ISONICOTINAMIDE'>I05</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">[[1sve\|1sve]], [[1svg\|1svg]], [[1svh\|1svh]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1sve\|1sve]], [[1svg\|1svg]], [[1svh\|1svh]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 ~~Bos taurus~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </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=1veb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1veb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1veb RCSB], [http://www.ebi.ac.uk/pdbsum/1veb 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=1veb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1veb OCA], [http://pdbe.org/1veb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1veb RCSB], [http://www.ebi.ac.uk/pdbsum/1veb PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 30:		Line 30:
	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 1veb" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[CAMP-dependent protein kinase\|CAMP-dependent protein kinase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bos taurus~~]]	+	[[Category: Bovin]]
-	[[Category: ~~Non-specific serine/threonine protein kinase~~]]	+	[[Category: Transferase]]
	[[Category: Berillon, L]]		[[Category: Berillon, L]]
	[[Category: Breitenlechner, C B]]		[[Category: Breitenlechner, C B]]
Line 50:		Line 54:
	[[Category: Kinase-inhibitor-complex]]		[[Category: Kinase-inhibitor-complex]]
	[[Category: Serine/threonine-protein kinase]]		[[Category: Serine/threonine-protein kinase]]
-	[[Category: Transferase]]

OCA at 09:30, 25 December 2014

OCA — Thu, 25 Dec 2014 09:30:49 GMT

←Older revision		Revision as of 09:30, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1veb]] 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=1VEB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1VEB FirstGlance]. <br>		<table><tr><td colspan='2'>[[1veb]] 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=1VEB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1VEB FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=I05:(3R,4R)-N-{4-[4-(2-FLUORO-6-HYDROXY-3-METHOXY-BENZOYL)-BENZYLOXY]-AZEPAN-3-YL}-ISONICOTINAMIDE'>I05</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=I05:(3R,4R)-N-{4-[4-(2-FLUORO-6-HYDROXY-3-METHOXY-BENZOYL)-BENZYLOXY]-AZEPAN-3-YL}-ISONICOTINAMIDE'>I05</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">[[1sve\|1sve]], [[1svg\|1svg]], [[1svh\|1svh]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1sve\|1sve]], [[1svg\|1svg]], [[1svh\|1svh]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus])</td></tr>
-	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1veb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1veb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1veb RCSB], [http://www.ebi.ac.uk/pdbsum/1veb 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=1veb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1veb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1veb RCSB], [http://www.ebi.ac.uk/pdbsum/1veb 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.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 28:		Line 30:
	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>
-
-	==See Also==
-	*[[CAMP-dependent protein kinase\|CAMP-dependent protein kinase]]
	== References ==		== References ==
	<references/>		<references/>
Line 37:		Line 36:
	[[Category: Bos taurus]]		[[Category: Bos taurus]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Berillon, L.]]	+	[[Category: Berillon, L]]
-	[[Category: Breitenlechner, C B.]]	+	[[Category: Breitenlechner, C B]]
-	[[Category: Engh, R A.]]	+	[[Category: Engh, R A]]
-	[[Category: Friebe, W G.]]	+	[[Category: Friebe, W G]]
-	[[Category: Graul, K.]]	+	[[Category: Graul, K]]
-	[[Category: Huber, R.]]	+	[[Category: Huber, R]]
-	[[Category: Marzenell, K.]]	+	[[Category: Marzenell, K]]
-	[[Category: Masjost, B.]]	+	[[Category: Masjost, B]]
-	[[Category: Schumacher, R.]]	+	[[Category: Schumacher, R]]
-	[[Category: Thomas, U.]]	+	[[Category: Thomas, U]]
-	[[Category: Wegge, T.]]	+	[[Category: Wegge, T]]
	[[Category: Balanol derivative]]		[[Category: Balanol derivative]]
	[[Category: Kinase-inhibitor-complex]]		[[Category: Kinase-inhibitor-complex]]
	[[Category: Serine/threonine-protein kinase]]		[[Category: Serine/threonine-protein kinase]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 20:38, 29 September 2014

OCA — Mon, 29 Sep 2014 20:38:15 GMT

←Older revision		Revision as of 20:38, 29 September 2014
Line 1:		Line 1:
-	[[~~Image:~~1veb.~~png~~\|~~left~~\|200px]]	+	==Crystal Structure of Protein Kinase A in Complex with Azepane Derivative 5==
		+	<StructureSection load='1veb' size='340' side='right' caption='[[1veb]], [[Resolution\|resolution]] 2.89Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1veb]] 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=1VEB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1VEB FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=I05:(3R,4R)-N-{4-[4-(2-FLUORO-6-HYDROXY-3-METHOXY-BENZOYL)-BENZYLOXY]-AZEPAN-3-YL}-ISONICOTINAMIDE'>I05</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">[[1sve\|1sve]], [[1svg\|1svg]], [[1svh\|1svh]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus])</td></tr>
		+	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1veb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1veb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1veb RCSB], [http://www.ebi.ac.uk/pdbsum/1veb PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ve/1veb_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Novel azepane derivatives were prepared and evaluated for protein kinase B (PKB-alpha) and protein kinase A (PKA) inhibition. The original (-)-balanol-derived lead structure (4R)-4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-benzoic acid (3R)-3-[(pyridine-4-carbonyl)amino]-azepan-4-yl ester (1) (IC(50) (PKB-alpha) = 5 nM) which contains an ester moiety was found to be plasma unstable and therefore unsuitable as a drug. Based upon molecular modeling studies using the crystal structure of the complex between PKA and 1, the five compounds N-[(3R,4R)-4-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-benzoylamino]-azepa n-3-yl]-isonicotinamide (4), (3R,4R)-N-[4-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-benzyloxy]-azepan-3 -yl]-isonicotinamide (5), N-[(3R,4S)-4-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-phenylamino]-methyl ]-azepan-3-yl)-isonicotinamide (6), N-[(3R,4R)-4-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-benzylamino]-azepan -3-yl]-isonicotinamide (7), and N-[(3R,4S)-4-(4-[trans-2-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-phenyl] -vinyl]-azepan-3-yl)-isonicotinamide (8) with linkers isosteric to the ester were designed, synthesized, and tested for in vitro inhibitory activity against PKA and PKB-alpha and for plasma stability in mouse plasma.(1) Compound 4 was found to be plasma stable and highly active (IC(50) (PKB-alpha) = 4 nM). Cocrystals with PKA were obtained for 4, 5, and 8 and analyzed for binding interactions and conformational changes in the ligands and protein in order to rationalize the different activities of the molecules.

-	~~{{STRUCTURE_1veb\| PDB=1veb \| SCENE= }}~~	+	Structure-based optimization of novel azepane derivatives as PKB inhibitors.,Breitenlechner CB, Wegge T, Berillon L, Graul K, Marzenell K, Friebe WG, Thomas U, Schumacher R, Huber R, Engh RA, Masjost B J Med Chem. 2004 Mar 11;47(6):1375-90. PMID:14998327<ref>PMID:14998327</ref>

-	~~===Crystal Structure~~ of ~~Protein Kinase A in Complex with Azepane Derivative 5===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_14998327}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[1veb]] 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=1VEB OCA].~~	+

	==See Also==		==See Also==
	*[[CAMP-dependent protein kinase\|CAMP-dependent protein kinase]]		*[[CAMP-dependent protein kinase\|CAMP-dependent protein kinase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:014998327<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Bos taurus]]		[[Category: Bos taurus]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]

OCA: Protected "1veb" [edit=sysop:move=sysop]

OCA — Sat, 05 Jan 2013 11:25:27 GMT

Protected "1veb" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:25, 5 January 2013

OCA at 11:25, 5 January 2013

OCA — Sat, 05 Jan 2013 11:25:25 GMT

←Older revision		Revision as of 11:25, 5 January 2013
Line 1:		Line 1:
-	{{Seed}}
	[[Image:1veb.png\|left\|200px]]		[[Image:1veb.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_1veb", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_1veb\| PDB=1veb \| SCENE= }}		{{STRUCTURE_1veb\| PDB=1veb \| SCENE= }}

	===Crystal Structure of Protein Kinase A in Complex with Azepane Derivative 5===		===Crystal Structure of Protein Kinase A in Complex with Azepane Derivative 5===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_14998327}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 14998327 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_14998327}}		{{ABSTRACT_PUBMED_14998327}}

	==About this Structure==		==About this Structure==
-	~~1VEB~~ is a 2 ~~chains~~ structure ~~of sequences~~ 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=1VEB OCA].	+	[[1veb]] 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=1VEB OCA].
		+
		+	==See Also==
		+	*[[CAMP-dependent protein kinase\|CAMP-dependent protein kinase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~14998327~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:014998327</ref><references group="xtra"/>
	[[Category: Bos taurus]]		[[Category: Bos taurus]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
Line 40:		Line 31:
	[[Category: Kinase-inhibitor-complex]]		[[Category: Kinase-inhibitor-complex]]
	[[Category: Serine/threonine-protein kinase]]		[[Category: Serine/threonine-protein kinase]]
-		+	[[Category: Transferase]]
-	~~''Page seeded by~~ [~~http~~:~~//oca.weizmann.ac.il/oca OCA~~ ] ~~on Tue Feb 17 12:43:18 2009''~~	+

OCA at 10:43, 17 February 2009

OCA — Tue, 17 Feb 2009 10:43:20 GMT

←Older revision		Revision as of 10:43, 17 February 2009
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	==About this Structure==		==About this Structure==
-	1VEB is a ~~[[Protein complex]]~~ structure of sequences 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=1VEB OCA].	+	1VEB is a 2 chains structure of sequences 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=1VEB OCA].

	==Reference==		==Reference==
-	Structure-based optimization of novel azepane derivatives as PKB inhibitors., Breitenlechner CB, Wegge T, Berillon L, Graul K, Marzenell K, Friebe WG, Thomas U, Schumacher R, Huber R, Engh RA, Masjost B, J Med Chem. 2004 Mar 11;47(6):1375-90. PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/14998327 14998327]~~	+	<ref group="xtra">PMID:14998327</ref><references group="xtra"/>
	[[Category: Bos taurus]]		[[Category: Bos taurus]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Protein complex]]
	[[Category: Berillon, L.]]		[[Category: Berillon, L.]]
	[[Category: Breitenlechner, C B.]]		[[Category: Breitenlechner, C B.]]
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	[[Category: Serine/threonine-protein kinase]]		[[Category: Serine/threonine-protein kinase]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Mon Jul 28~~ 17:07:~~09 2008~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 12:43:18 2009''