2gfc

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[[Image:2gfc.gif|left|200px]]
 
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{{Structure
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==cAMP-dependent protein kinase PKA catalytic subunit with PKI-5-24==
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|PDB= 2gfc |SIZE=350|CAPTION= <scene name='initialview01'>2gfc</scene>, resolution 1.87&Aring;
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<StructureSection load='2gfc' size='340' side='right'caption='[[2gfc]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=OCT:N-OCTANE'>OCT</scene>
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<table><tr><td colspan='2'>[[2gfc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GFC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GFC FirstGlance]. <br>
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|ACTIVITY= [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.87&#8491;</td></tr>
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|GENE= PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OCT:N-OCTANE'>OCT</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
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}}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2gfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gfc OCA], [https://pdbe.org/2gfc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gfc RCSB], [https://www.ebi.ac.uk/pdbsum/2gfc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gfc ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/IPKA_RABIT IPKA_RABIT] 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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gf/2gfc_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2gfc ConSurf].
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<div style="clear:both"></div>
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'''cAMP-dependent protein kinase PKA catalytic subunit with PKI-5-24'''
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==See Also==
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*[[CAMP-dependent protein kinase 3D structures|CAMP-dependent protein kinase 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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Controlling aberrant kinase-mediated cellular signaling is a major strategy in cancer therapy; successful protein kinase inhibitors such as Tarceva and Gleevec verify this approach. Specificity of inhibitors for the targeted kinase(s), however, is a crucial factor for therapeutic success. Based on homology modeling, we previously identified four amino acids in the active site of Rho-kinase that likely determine inhibitor specificities observed for Rho-kinase relative to protein kinase A (PKA) (in PKA numbering: T183A, L49I, V123M, and E127D), and a fifth (Q181K) that played a surprising role in PKA-PKB hybrid proteins. We have systematically mutated these residues in PKA to their counterparts in Rho-kinase, individually and in combination. Using four Rho-kinase-specific, one PKA-specific, and one pan-kinase-specific inhibitor, we measured the inhibitor-binding properties of the mutated proteins and identify the roles of individual residues as specificity determinants. Two combined mutant proteins, containing the combination of mutations T183A and L49I, closely mimic Rho-kinase. Kinetic results corroborate the hypothesis that side-chain identities form the major determinants of selectivity. An unexpected result of the analysis is the consistent contribution of the individual mutations by simple factors. Crystal structures of the surrogate kinase inhibitor complexes provide a detailed basis for an understanding of these selectivity determinant residues. The ability to obtain kinetic and structural data from these PKA mutants, combined with their Rho-kinase-like selectivity profiles, make them valuable for use as surrogate kinases for structure-based inhibitor design.
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==About this Structure==
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2GFC is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GFC OCA].
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==Reference==
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Structural analysis of protein kinase A mutants with Rho-kinase inhibitor specificity., Bonn S, Herrero S, Breitenlechner CB, Erlbruch A, Lehmann W, Engh RA, Gassel M, Bossemeyer D, J Biol Chem. 2006 Aug 25;281(34):24818-30. Epub 2006 May 12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16699172 16699172]
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[[Category: Bos taurus]]
[[Category: Bos taurus]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Large Structures]]
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[[Category: Protein complex]]
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[[Category: Oryctolagus cuniculus]]
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[[Category: Bonn, S.]]
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[[Category: Bonn S]]
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[[Category: Bossemeyer, D.]]
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[[Category: Bossemeyer D]]
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[[Category: Breitenlechner, C B.]]
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[[Category: Breitenlechner CB]]
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[[Category: Engh, R A.]]
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[[Category: Engh RA]]
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[[Category: Gassel, M.]]
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[[Category: Gassel M]]
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[[Category: Herrero, S.]]
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[[Category: Herrero S]]
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[[Category: OCT]]
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[[Category: binary complex]]
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[[Category: peptide inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:04:01 2008''
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Current revision

cAMP-dependent protein kinase PKA catalytic subunit with PKI-5-24

PDB ID 2gfc

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