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| | ==Low temperature X-ray structure of cAMP dependent Protein Kinase A catalytic subunit with low Mg2+, ATP and IP20== | | ==Low temperature X-ray structure of cAMP dependent Protein Kinase A catalytic subunit with low Mg2+, ATP and IP20== |
| - | <StructureSection load='4dh1' size='340' side='right' caption='[[4dh1]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4dh1' size='340' side='right'caption='[[4dh1]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4dh1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DH1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DH1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4dh1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DH1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DH1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4dh1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dh1 OCA], [https://pdbe.org/4dh1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dh1 RCSB], [https://www.ebi.ac.uk/pdbsum/4dh1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dh1 ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dh3|4dh3]], [[4dh5|4dh5]], [[4dh7|4dh7]], [[4dh8|4dh8]]</td></tr>
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| - | <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 Mus musculus])</td></tr>
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| - | <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=4dh1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dh1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dh1 RCSB], [http://www.ebi.ac.uk/pdbsum/4dh1 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [[https://www.uniprot.org/uniprot/IPKA_MOUSE 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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4dh1" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[CAMP-dependent protein kinase|CAMP-dependent protein kinase]] | + | *[[CAMP-dependent protein kinase 3D structures|CAMP-dependent protein kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: CAMP-dependent protein kinase]]
| + | [[Category: Kovalevsky AY]] |
| - | [[Category: Kovalevsky, A Y]] | + | [[Category: Langan P]] |
| - | [[Category: Langan, P]] | + | |
| - | [[Category: Peptidic inhibitor]]
| + | |
| - | [[Category: Phosphorylation]]
| + | |
| - | [[Category: Protein kinase]]
| + | |
| - | [[Category: Transferase-transferase inhibitor complex]]
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| Structural highlights
Function
[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.
Publication Abstract from PubMed
Post-translational protein phosphorylation by protein kinase A (PKA) is a ubiquitous signalling mechanism which regulates many cellular processes. A low-temperature X-ray structure of the ternary complex of the PKA catalytic subunit (PKAc) with ATP and a 20-residue peptidic inhibitor (IP20) at the physiological Mg(2+) concentration of approximately 0.5 mM (LT PKA-MgATP-IP20) revealed a single metal ion in the active site. The lack of a second metal in LT PKA-MgATP-IP20 renders the beta- and gamma-phosphoryl groups of ATP very flexible, with high thermal B factors. Thus, the second metal is crucial for tight positioning of the terminal phosphoryl group for transfer to a substrate, as demonstrated by comparison of the former structure with that of the LT PKA-Mg(2)ATP-IP20 complex obtained at high Mg(2+) concentration. In addition to its kinase activity, PKAc is also able to slowly catalyze the hydrolysis of ATP using a water molecule as a substrate. It was found that ATP can be readily and completely hydrolyzed to ADP and a free phosphate ion in the crystals of the ternary complex PKA-Mg(2)ATP-IP20 by X-ray irradiation at room temperature. The cleavage of ATP may be aided by X-ray-generated free hydroxyl radicals, a very reactive chemical species, which move rapidly through the crystal at room temperature. The phosphate anion is clearly visible in the electron-density maps; it remains in the active site but slides about 2 A from its position in ATP towards Ala21 of IP20, which mimics the phosphorylation site. The phosphate thus pushes the peptidic inhibitor away from the product ADP, while resulting in dramatic conformational changes of the terminal residues 24 and 25 of IP20. X-ray structures of PKAc in complex with the nonhydrolysable ATP analogue AMP-PNP at both room and low temperature demonstrated no temperature effects on the conformation and position of IP20.
Low- and room-temperature X-ray structures of protein kinase A ternary complexes shed new light on its activity.,Kovalevsky AY, Johnson H, Hanson BL, Waltman MJ, Fisher SZ, Taylor S, Langan P Acta Crystallogr D Biol Crystallogr. 2012 Jul;68(Pt 7):854-60. doi:, 10.1107/S0907444912014886. Epub 2012 Jun 15. PMID:22751671[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kovalevsky AY, Johnson H, Hanson BL, Waltman MJ, Fisher SZ, Taylor S, Langan P. Low- and room-temperature X-ray structures of protein kinase A ternary complexes shed new light on its activity. Acta Crystallogr D Biol Crystallogr. 2012 Jul;68(Pt 7):854-60. doi:, 10.1107/S0907444912014886. Epub 2012 Jun 15. PMID:22751671 doi:http://dx.doi.org/10.1107/S0907444912014886
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