View source for 1ctp


==STRUCTURE OF THE MAMMALIAN CATALYTIC SUBUNIT OF CAMP-DEPENDENT PROTEIN KINASE AND AN INHIBITOR PEPTIDE DISPLAYS AN OPEN CONFORMATION==
<StructureSection load='1ctp' size='340' side='right' caption='[[1ctp]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ctp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Pig Pig]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CTP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1CTP FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>, <scene name='pdbligand=TYI:3,5-DIIODOTYROSINE'>TYI</scene></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=1ctp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ctp OCA], [http://pdbe.org/1ctp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ctp RCSB], [http://www.ebi.ac.uk/pdbsum/1ctp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ctp ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/KAPCA_PIG KAPCA_PIG]] 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 ==
[[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/ct/1ctp_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/main_output.php?pdb_ID=1ctp ConSurf].
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== Publication Abstract from PubMed ==
The crystal structure of a binary complex of the porcine heart catalytic (C) subunit of cAMP-dependent protein kinase (space group P4(1)32; a = 171.5 A) complexed with a di-iodinated peptide inhibitor, PKI(5-24), has been solved and refined to 2.9 A resolution with an overall R of 21.1%. The r.m.s. deviations from ideal bond lengths and angles are 0.022 A and 4.3 degrees. A single isotropic B of 17 A(2) was used for all atoms. The structure solution was carried out initially by molecular replacement of electron density followed by refinement against atomic coordinates from orthorhombic crystals of a binary complex of the mouse recombinant enzyme previously described [Knighton, Zheng, Ten Eyck, Ashford, Xuong, Taylor &amp; Sowadski (1991). Science, 253, 407-414]. The most striking difference between the two crystal structures is a large displacement of the small lobe of the enzyme. In the cubic crystal, the beta-sheet of the small lobe is rotated by 15 degrees and translated by 1.9 A with respect to the orthorhombic crystal. Possible explanations for why this binary complex crystallized in an open conformation in contrast to a similar binary complex of the recombinant enzyme are discussed. This study demonstrates that considerable information about parts of a crystal structure can be obtained without a complete crystal structure analysis. Specifically, the six rigid-group parameters of a poly alanine model of the beta-structure were obtained satisfactorily from a crystal structure by refinement of difference Fourier coefficients based on an approximate partial structure model.

Structure of the mammalian catalytic subunit of cAMP-dependent protein kinase and an inhibitor peptide displays an open conformation.,Karlsson R, Zheng J, Xuong N, Taylor SS, Sowadski JM Acta Crystallogr D Biol Crystallogr. 1993 Jul 1;49(Pt 4):381-8. PMID:15299513<ref>PMID:15299513</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Pig]]
[[Category: Transferase]]
[[Category: Karlsson, R]]
[[Category: Sowadski, J M]]
[[Category: Taylor, S S]]
[[Category: Xuong, N H]]
[[Category: Zheng, J]]
[[Category: Transferase-transferase inhibitor complex]]