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3fjq

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Revision as of 06:43, 1 November 2017

Crystal structure of cAMP-dependent protein kinase catalytic subunit alpha in complex with peptide inhibitor PKI alpha (6-25)

Structural highlights

3fjq is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:	,
Gene:	Prkaca, Pkaca (LK3 transgenic mice), Pkia (LK3 transgenic mice)
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] [IPKA_MOUSE] 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

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

Publication Abstract from PubMed

Identifying conserved pockets on the surfaces of a family of proteins can provide insight into conserved geometric features and sites of protein-protein interaction. Here we describe mapping and comparison of the surfaces of aligned crystallographic structures, using the protein kinase family as a model. Pockets are rapidly computed using two computer programs, FADE and Crevasse. FADE uses gradients of atomic density to locate grooves and pockets on the molecular surface. Crevasse, a new piece of software, splits the FADE output into distinct pockets. The computation was run on ten kinase catalytic cores aligned on the alphaF-helix, and the resulting pockets spatially clustered. The active site cleft appears as a large, contiguous site that can be subdivided into nucleotide and substrate docking sites. Substrate specificity determinants in the active site cleft between serine/threonine and tyrosine kinases are visible and distinct. The active site clefts cluster tightly, showing a conserved spatial relationship between the active site and alphaF-helix in the C-lobe. When the alphaC-helix is examined, there are multiple mechanisms for anchoring the helix using spatially conserved docking sites. A novel site at the top of the N-lobe is present in all the kinases, and there is a large conserved pocket over the hinge and the alphaC-beta4 loop. Other pockets on the kinase core are strongly conserved but have not yet been mapped to a protein-protein interaction. Sites identified by this algorithm have revealed structural and spatially conserved features of the kinase family and potential conserved inter- and intra-molecular binding sites.

Comparative surface geometry of the protein kinase family.,Thompson EE, Kornev AP, Kannan N, Kim C, Ten Eyck LF, Taylor SS Protein Sci. 2009 Jul 16. PMID:19610074^[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
↑ Thompson EE, Kornev AP, Kannan N, Kim C, Ten Eyck LF, Taylor SS. Comparative surface geometry of the protein kinase family. Protein Sci. 2009 Jul 16. PMID:19610074 doi:10.1002/pro.209

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/3fjq"

@@ Line 1: / Line 1: @@
 ==Crystal structure of cAMP-dependent protein kinase catalytic subunit alpha in complex with peptide inhibitor PKI alpha (6-25)==
 <StructureSection load='3fjq' size='340' side='right' caption='[[3fjq]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <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]), Pkia ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/cAMP-dependent_protein_kinase cAMP-dependent protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.11 2.7.11.11] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3fjq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fjq OCA], [http://pdbe.org/3fjq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fjq RCSB], [http://www.ebi.ac.uk/pdbsum/3fjq 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=3fjq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fjq OCA], [http://pdbe.org/3fjq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fjq RCSB], [http://www.ebi.ac.uk/pdbsum/3fjq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fjq ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 30: / Line 31: @@
 </div>
 <div class="pdbe-citations 3fjq" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[CAMP-dependent protein kinase|CAMP-dependent protein kinase]]
 == References ==
 <references/>
@@ Line 40: / Line 38: @@
 [[Category: CAMP-dependent protein kinase]]
 [[Category: Kim, C]]
+[[Category: Alternative splicing]]
 [[Category: Atp binding]]
 [[Category: Atp-binding]]
 [[Category: Camp]]
 [[Category: Camp-dependent protein kinase activity]]
+[[Category: Cytoplasm]]
 [[Category: Kinase]]
 [[Category: Kinase activity]]

3fjq

From Proteopedia

Revision as of 06:43, 1 November 2017

Crystal structure of cAMP-dependent protein kinase catalytic subunit alpha in complex with peptide inhibitor PKI alpha (6-25)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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