4o22

From Proteopedia

(Difference between revisions)

Revision as of 08:27, 10 April 2019

Binary complex of metal-free PKAc with SP20.

Structural highlights

4o22 is a 2 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:	,
Related:	4o21
Gene:	Pkaca, Prkaca, Prkaca Pkaca (LK3 transgenic mice), PKIA, PKIA PRKACN1, PRKACN1 (HUMAN)
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_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.

Publication Abstract from PubMed

X-ray structures of several ternary product complexes of the catalytic subunit of cAMP-dependent protein kinase (PKAc) have been determined with no bound metal ions and with Na(+) or K(+) coordinated at two metal-binding sites. The metal-free PKAc and the enzyme with alkali metals were able to facilitate the phosphoryl transfer reaction. In all studied complexes, the ATP and the substrate peptide (SP20) were modified into the products ADP and the phosphorylated peptide. The products of the phosphotransfer reaction were also found when ATP-gammaS, a nonhydrolyzable ATP analogue, reacted with SP20 in the PKAc active site containing no metals. Single turnover enzyme kinetics measurements utilizing (32)P-labeled ATP confirmed the phosphotransferase activity of the enzyme in the absence of metal ions and in the presence of alkali metals. In addition, the structure of the apo-PKAc binary complex with SP20 suggests that the sequence of binding events may become ordered in a metal-free environment, with SP20 binding first to prime the enzyme for subsequent ATP binding. Comparison of these structures reveals conformational and hydrogen bonding changes that might be important for the mechanism of catalysis.

Metal-Free cAMP-Dependent Protein Kinase Can Catalyze Phosphoryl Transfer.,Gerlits O, Das A, Keshwani MM, Taylor S, Waltman MJ, Langan P, Heller WT, Kovalevsky A Biochemistry. 2014 May 20;53(19):3179-86. doi: 10.1021/bi5000965. Epub 2014 May, 8. PMID:24786636^[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
↑ Gerlits O, Das A, Keshwani MM, Taylor S, Waltman MJ, Langan P, Heller WT, Kovalevsky A. Metal-Free cAMP-Dependent Protein Kinase Can Catalyze Phosphoryl Transfer. Biochemistry. 2014 May 20;53(19):3179-86. doi: 10.1021/bi5000965. Epub 2014 May, 8. PMID:24786636 doi:http://dx.doi.org/10.1021/bi5000965

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4o22"

@@ Line 1: / Line 1: @@
 ==Binary complex of metal-free PKAc with SP20.==
-<StructureSection load='4o22' size='340' side='right' caption='[[4o22]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+<StructureSection load='4o22' size='340' side='right'caption='[[4o22]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4o22]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O22 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O22 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4o22]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O22 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O22 FirstGlance]. <br>
 </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">[[4o21|4o21]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Pkaca, Prkaca, Prkaca Pkaca ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), PKIA, PKIA PRKACN1, PRKACN1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4o22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o22 OCA], [http://pdbe.org/4o22 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o22 RCSB], [http://www.ebi.ac.uk/pdbsum/4o22 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o22 ProSAT]</span></td></tr>
@@ Line 27: / Line 28: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: CAMP-dependent protein kinase]]
 [[Category: Das, A]]

4o22

From Proteopedia

Revision as of 08:27, 10 April 2019

Binary complex of metal-free PKAc with SP20.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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