2qcs

From Proteopedia

(Difference between revisions)

Revision as of 09:43, 18 October 2017

A complex structure between the Catalytic and Regulatory subunit of Protein Kinase A that represents the inhibited state

Structural highlights

2qcs is a 2 chain structure with sequence from Bovin and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , ,
NonStd Res:	,
Related:	1apm, 1rgs, 1ne6, 1ne4
Gene:	Prkaca, Pkaca (LK3 transgenic mice), PRKAR1A (BOVIN)
Activity:	cAMP-dependent protein kinase, with EC number 2.7.11.11
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[KAPCA_MOUSE] Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, TRPC1 and VASP. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). TRPC1 activation by phosphorylation promotes Ca(2+) influx, essential for the increase in permeability induced by thrombin in confluent endothelial monolayers. PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Regulates negatively tight junction (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT).^[1] ^[2] ^[3] [KAP0_BOVIN] Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Protein kinase A (PKA) holoenzyme is one of the major receptors for cyclic adenosine monophosphate (cAMP), where an extracellular stimulus is translated into a signaling response. We report here the structure of a complex between the PKA catalytic subunit and a mutant RI regulatory subunit, RIalpha(91-379:R333K), containing both cAMP-binding domains. Upon binding to the catalytic subunit, RI undergoes a dramatic conformational change in which the two cAMP-binding domains uncouple and wrap around the large lobe of the catalytic subunit. This large conformational reorganization reveals the concerted mechanism required to bind and inhibit the catalytic subunit. The structure also reveals a holoenzyme-specific salt bridge between two conserved residues, Glu261 and Arg366, that tethers the two adenine capping residues far from their cAMP-binding sites. Mutagenesis of these residues demonstrates their importance for PKA activation. Our structural insights, combined with the mutagenesis results, provide a molecular mechanism for the ordered and cooperative activation of PKA by cAMP.

PKA-I holoenzyme structure reveals a mechanism for cAMP-dependent activation.,Kim C, Cheng CY, Saldanha SA, Taylor SS Cell. 2007 Sep 21;130(6):1032-43. PMID:17889648^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Nolan MA, Babcock DF, Wennemuth G, Brown W, Burton KA, McKnight GS. Sperm-specific protein kinase A catalytic subunit Calpha2 orchestrates cAMP signaling for male fertility. Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13483-8. Epub 2004 Aug 31. PMID:15340140 doi:10.1073/pnas.0405580101
↑ Pirino G, Wescott MP, Donovan PJ. Protein kinase A regulates resumption of meiosis by phosphorylation of Cdc25B in mammalian oocytes. Cell Cycle. 2009 Feb 15;8(4):665-70. Epub 2009 Feb 14. PMID:19223768
↑ Baker MA, Hetherington L, Curry B, Aitken RJ. Phosphorylation and consequent stimulation of the tyrosine kinase c-Abl by PKA in mouse spermatozoa; its implications during capacitation. Dev Biol. 2009 Sep 1;333(1):57-66. doi: 10.1016/j.ydbio.2009.06.022. Epub 2009, Jun 26. PMID:19560455 doi:10.1016/j.ydbio.2009.06.022
↑ Kim C, Cheng CY, Saldanha SA, Taylor SS. PKA-I holoenzyme structure reveals a mechanism for cAMP-dependent activation. Cell. 2007 Sep 21;130(6):1032-43. PMID:17889648 doi:10.1016/j.cell.2007.07.018

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2qcs"

@@ Line 1: / Line 1: @@
 ==A complex structure between the Catalytic and Regulatory subunit of Protein Kinase A that represents the inhibited state==
 <StructureSection load='2qcs' size='340' side='right' caption='[[2qcs]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
@@ Line 8: / Line 9: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Prkaca, Pkaca ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), PRKAR1A ([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/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=2qcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qcs OCA], [http://pdbe.org/2qcs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qcs RCSB], [http://www.ebi.ac.uk/pdbsum/2qcs 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=2qcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qcs OCA], [http://pdbe.org/2qcs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qcs RCSB], [http://www.ebi.ac.uk/pdbsum/2qcs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2qcs ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 31: / Line 32: @@
 </div>
 <div class="pdbe-citations 2qcs" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[CAMP-dependent protein kinase|CAMP-dependent protein kinase]]
 == References ==
 <references/>

2qcs

From Proteopedia

Revision as of 09:43, 18 October 2017

A complex structure between the Catalytic and Regulatory subunit of Protein Kinase A that represents the inhibited state

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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