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[[Image:2izx.jpg|left|200px]]<br /><applet load="2izx" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2izx, resolution 1.30&Aring;" />
'''MOLECULAR BASIS OF AKAP SPECIFICITY FOR PKA REGULATORY SUBUNITS'''<br />


==Overview==
==Molecular Basis of AKAP Specificity for PKA Regulatory Subunits==
Localization of cyclic AMP (cAMP)-dependent protein kinase (PKA) by A, kinase-anchoring proteins (AKAPs) restricts the action of this broad, specificity kinase. The high-resolution crystal structures of the docking, and dimerization (D/D) domain of the RIIalpha regulatory subunit of PKA, both in the apo state and in complex with the high-affinity anchoring, peptide AKAP-IS explain the molecular basis for AKAP-regulatory subunit, recognition. AKAP-IS folds into an amphipathic alpha helix that engages an, essentially preformed shallow groove on the surface of the RII dimer D/D, domains. Conserved AKAP aliphatic residues dominate interactions to RII at, the predominantly hydrophobic interface, whereas polar residues are, important in conferring R subunit isoform specificity. Using a peptide, screening approach, we have developed SuperAKAP-IS, a peptide that is, 10,000-fold more selective for the RII isoform relative to RI and can be, used to assess the impact of PKA isoform-selective anchoring on, cAMP-responsive events inside cells.
<StructureSection load='2izx' size='340' side='right'caption='[[2izx]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2izx]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IZX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IZX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTD:DITHIANE+DIOL'>DTD</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=2izx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2izx OCA], [https://pdbe.org/2izx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2izx RCSB], [https://www.ebi.ac.uk/pdbsum/2izx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2izx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KAP2_HUMAN KAP2_HUMAN] Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase.
== 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/iz/2izx_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=2izx ConSurf].
<div style="clear:both"></div>


==Disease==
==See Also==
Known disease associated with this structure: Kallmann syndrome 3 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607123 607123]]
*[[CAMP-dependent protein kinase 3D structures|CAMP-dependent protein kinase 3D structures]]
 
__TOC__
==About this Structure==
</StructureSection>
2IZX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with DTD as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Known structural/functional Site: <scene name='pdbsite=AC1:Dtd Binding Site For Chain A'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2IZX OCA].
 
==Reference==
Molecular basis of AKAP specificity for PKA regulatory subunits., Gold MG, Lygren B, Dokurno P, Hoshi N, McConnachie G, Tasken K, Carlson CR, Scott JD, Barford D, Mol Cell. 2006 Nov 3;24(3):383-95. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17081989 17081989]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: cAMP-dependent protein kinase]]
[[Category: Synthetic construct]]
[[Category: Barford, D.]]
[[Category: Barford D]]
[[Category: Carlson, C.R.]]
[[Category: Carlson CR]]
[[Category: Dokurno, P.]]
[[Category: Dokurno P]]
[[Category: Gold, M.G.]]
[[Category: Gold MG]]
[[Category: Hoshi, N.]]
[[Category: Hoshi N]]
[[Category: Lygren, B.]]
[[Category: Lygren B]]
[[Category: Mcconnachie, G.]]
[[Category: McConnachie G]]
[[Category: Scott, J.D.]]
[[Category: Scott JD]]
[[Category: Tasken, K.]]
[[Category: Tasken K]]
[[Category: DTD]]
[[Category: acetylation]]
[[Category: akap]]
[[Category: anchor]]
[[Category: camp]]
[[Category: camp-binding]]
[[Category: kinase]]
[[Category: nucleotide-binding]]
[[Category: phosphorylation]]
[[Category: pka]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 19:41:56 2007''

Latest revision as of 09:41, 1 May 2024

Molecular Basis of AKAP Specificity for PKA Regulatory SubunitsMolecular Basis of AKAP Specificity for PKA Regulatory Subunits

Structural highlights

2izx is a 3 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.3Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KAP2_HUMAN Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase.

Evolutionary Conservation

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

See Also

2izx, resolution 1.30Å

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OCA
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