6ync - Revision history

OCA at 09:18, 9 October 2024

2024-10-09T09:18:11Z

← Older revision		Revision as of 09:18, 9 October 2024
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	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ync FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ync OCA], [https://pdbe.org/6ync PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ync RCSB], [https://www.ebi.ac.uk/pdbsum/6ync PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ync 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=6ync FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ync OCA], [https://pdbe.org/6ync PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ync RCSB], [https://www.ebi.ac.uk/pdbsum/6ync PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ync ProSAT]</span></td></tr>
	</table>		</table>
	~~== Function ==~~
	[https://www.uniprot.org/uniprot/KAPCA_CRIGR KAPCA_CRIGR] 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 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+). PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Negatively regulates tight junctions (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. 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). Phosphorylates APOBEC3G and AICDA (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 13:31, 24 January 2024

2024-01-24T13:31:05Z

← Older revision		Revision as of 13:31, 24 January 2024
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	====		==Crystal structure of cAMP-dependent Protein Kinase (PKA) in complex with the methylated Fasudil-derived fragment N-methylisoquinoline-5-sulfonamide (soaked)==
	<StructureSection load='6ync' size='340' side='right'caption='[[6ync]]' scene=''>		<StructureSection load='6ync' size='340' side='right'caption='[[6ync]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>		<table><tr><td colspan='2'>[[6ync]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cricetulus_griseus Cricetulus griseus] 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=6YNC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YNC FirstGlance]. <br>
	</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=6ync FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ync OCA], [~~http~~://pdbe.org/6ync PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6ync RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6ync PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6ync ProSAT]</span></td></tr>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.4Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7CT:~{N}-methylisoquinoline-5-sulfonamide'>7CT</scene>, <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=6ync FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ync OCA], [https://pdbe.org/6ync PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ync RCSB], [https://www.ebi.ac.uk/pdbsum/6ync PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ync ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[https://www.uniprot.org/uniprot/KAPCA_CRIGR KAPCA_CRIGR] 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 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+). PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Negatively regulates tight junctions (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. 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). Phosphorylates APOBEC3G and AICDA (By similarity).
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			In lead optimization, protein crystallography is an indispensable tool to analyze drug binding. Binding modes and non-covalent interaction inventories are essential to design follow-up synthesis candidates. Two protocols are commonly applied to produce protein-ligand complexes: cocrystallization and soaking. Because of its time and cost effectiveness, soaking is the more popular method. Taking eight ligand hinge binders of protein kinase A, we demonstrate that cocrystallization is superior. Particularly for flexible proteins, such as kinases, and larger ligands cocrystallization captures more reliable the correct binding pose and induced protein adaptations. The geometrical discrepancies between soaking and cocrystallization appear smaller for fragment-sized ligands. For larger flexible ligands that trigger conformational changes of the protein, soaking can be misleading and underestimates the number of possible polar interactions due to inadequate, highly impaired positions of protein amino-acid side and main chain atoms. Thus, if applicable cocrystallization should be the gold standard to study protein-ligand complexes.

			Two Methods, one Goal: Structural Differences between Cocrystallization and Crystal Soaking to Discover Ligand Binding Poses.,Klebe G, Wienen-Schmidt B, Oebbeke M, Ngo K, Heine A ChemMedChem. 2020 Oct 8. doi: 10.1002/cmdc.202000565. PMID:33029876<ref>PMID:33029876</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 6ync" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[CAMP-dependent protein kinase 3D structures\|CAMP-dependent protein kinase 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Cricetulus griseus]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Z-~~disk~~]]		[[Category: Mus musculus]]
			[[Category: Heine A]]
			[[Category: Klebe G]]
			[[Category: Oebbeke M]]
			[[Category: Wienen-Schmidt B]]

OCA at 05:50, 14 October 2020

2020-10-14T05:50:00Z

← Older revision		Revision as of 05:50, 14 October 2020
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	~~'''Unreleased structure'''~~

	~~The entry~~ 6ync ~~is ON HOLD until Paper Publication~~		====
			<StructureSection load='6ync' size='340' side='right'caption='[[6ync]]' scene=''>
	~~Authors~~: ~~Oebbeke, M~~.~~, Wienen~~-~~Schmidt, B~~.~~, Heine, A~~.~~, Klebe, G~~.		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
	~~Description~~: ~~Crystal structure of cAMP-dependent Protein Kinase (PKA) in complex with the methylated Fasudil-derived fragment N-methylisoquinoline-5-sulfonamide (soaked)~~		</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=6ync FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ync OCA], [http://pdbe.org/6ync PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ync RCSB], [http://www.ebi.ac.uk/pdbsum/6ync PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ync ProSAT]</span></td></tr>
	[~~[Category~~: ~~Unreleased Structures~~]]		</table>
	[~~[Category~~: ~~Wienen~~-~~Schmidt~~, B]]		__TOC__
	[[~~Category~~: ~~Klebe, G]~~]		</StructureSection>
	[[Category: ~~Heine, A~~]]		[[Category: Large Structures]]
	[[Category: ~~Oebbeke, M~~]]		[[Category: Z-disk]]

OCA at 05:22, 29 April 2020

2020-04-29T05:22:59Z

← Older revision		Revision as of 05:22, 29 April 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 6ync is ON HOLD		The entry 6ync is ON HOLD until Paper Publication

	Authors: Oebbeke, M., Wienen-Schmidt, B., Heine, A., Klebe, G.		Authors: Oebbeke, M., Wienen-Schmidt, B., Heine, A., Klebe, G.
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	Description: Crystal structure of cAMP-dependent Protein Kinase (PKA) in complex with the methylated Fasudil-derived fragment N-methylisoquinoline-5-sulfonamide (soaked)		Description: Crystal structure of cAMP-dependent Protein Kinase (PKA) in complex with the methylated Fasudil-derived fragment N-methylisoquinoline-5-sulfonamide (soaked)
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
			[[Category: Wienen-Schmidt, B]]
			[[Category: Klebe, G]]
	[[Category: Heine, A]]		[[Category: Heine, A]]
	~~[[Category: Wienen-Schmidt, B]]~~
	[[Category: Oebbeke, M]]		[[Category: Oebbeke, M]]
	~~[[Category: Klebe, G]]~~

OCA: Protected "6ync" [edit=sysop:move=sysop]

2020-04-22T04:23:48Z

Protected "6ync" [edit=sysop:move=sysop]

← Older revision	Revision as of 04:23, 22 April 2020
(No difference)

OCA: New page: '''Unreleased structure''' The entry 6ync is ON HOLD Authors: Oebbeke, M., Wienen-Schmidt, B., Heine, A., Klebe, G. Description: Crystal structure of cAMP-dependent Protein Kinase (PKA...

2020-04-22T04:23:46Z

New page: '''Unreleased structure''' The entry 6ync is ON HOLD Authors: Oebbeke, M., Wienen-Schmidt, B., Heine, A., Klebe, G. Description: Crystal structure of cAMP-dependent Protein Kinase (PKA...

New page

'''Unreleased structure'''

The entry 6ync is ON HOLD

Authors: Oebbeke, M., Wienen-Schmidt, B., Heine, A., Klebe, G.

Description: Crystal structure of cAMP-dependent Protein Kinase (PKA) in complex with the methylated Fasudil-derived fragment N-methylisoquinoline-5-sulfonamide (soaked)
[[Category: Unreleased Structures]]
[[Category: Heine, A]]
[[Category: Wienen-Schmidt, B]]
[[Category: Oebbeke, M]]
[[Category: Klebe, G]]