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| | <StructureSection load='5kjy' size='340' side='right'caption='[[5kjy]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='5kjy' size='340' side='right'caption='[[5kjy]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5kjy]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KJY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KJY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5kjy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KJY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KJY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CMP:ADENOSINE-3,5-CYCLIC-MONOPHOSPHATE'>CMP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kjz|5kjz]], [[5kjx|5kjx]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CMP:ADENOSINE-3,5-CYCLIC-MONOPHOSPHATE'>CMP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRKAR1A, PKR1, PRKAR1, TSE1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5kjy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kjy OCA], [https://pdbe.org/5kjy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kjy RCSB], [https://www.ebi.ac.uk/pdbsum/5kjy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kjy ProSAT]</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=5kjy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kjy OCA], [http://pdbe.org/5kjy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kjy RCSB], [http://www.ebi.ac.uk/pdbsum/5kjy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kjy ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/KAP0_HUMAN KAP0_HUMAN]] Acute promyelocytic leukemia;Acrodysostosis with multiple hormone resistance;Familial atrial myxoma;Primary pigmented nodular adrenocortical disease;Carney complex;Acrodysostosis. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/KAP0_HUMAN KAP0_HUMAN] Acute promyelocytic leukemia;Acrodysostosis with multiple hormone resistance;Familial atrial myxoma;Primary pigmented nodular adrenocortical disease;Carney complex;Acrodysostosis. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KAP0_HUMAN KAP0_HUMAN]] Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.<ref>PMID:16491121</ref> <ref>PMID:20215566</ref> <ref>PMID:26405036</ref> | + | [https://www.uniprot.org/uniprot/KAP0_HUMAN KAP0_HUMAN] Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.<ref>PMID:16491121</ref> <ref>PMID:20215566</ref> <ref>PMID:26405036</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Herberg, F W]] | + | [[Category: Herberg FW]] |
| - | [[Category: Huang, G Y]] | + | [[Category: Huang GY]] |
| - | [[Category: Kim, C]] | + | [[Category: Kim C]] |
| - | [[Category: Kim, J J]] | + | [[Category: Kim JJ]] |
| - | [[Category: Lorenz, R]] | + | [[Category: Lorenz R]] |
| - | [[Category: Moon, E]] | + | [[Category: Moon E]] |
| - | [[Category: Camp-dependent protein kinase]]
| + | |
| - | [[Category: Cyclic nucleotide]]
| + | |
| - | [[Category: Cyclic nucleotide binding domain]]
| + | |
| - | [[Category: Nucleotide selectivity]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Disease
KAP0_HUMAN Acute promyelocytic leukemia;Acrodysostosis with multiple hormone resistance;Familial atrial myxoma;Primary pigmented nodular adrenocortical disease;Carney complex;Acrodysostosis. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
KAP0_HUMAN Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.[1] [2] [3]
Publication Abstract from PubMed
Cyclic AMP and cyclic GMP are ubiquitous second messengers that regulate the activity of effector proteins in all forms of life. The main effector proteins, the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and the 3',5'-cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG), are preferentially activated by cAMP and cGMP, respectively. However, the molecular basis of this cyclic nucleotide selectivity is still not fully understood. Analysis of isolated cyclic nucleotide-binding (CNB) domains of PKA regulatory subunit type Ialpha (RIalpha) reveals that the C-terminal CNB-B has a higher cAMP affinity and selectivity than the N-terminal CNB-A. Here, we show that introducing cGMP-specific residues using site-directed mutagenesis reduces the selectivity of CNB-B, while the combination of two mutations (G316R/A336T) results in a cGMP-selective binding domain. Furthermore, introducing the corresponding mutations (T192R/A212T) into the PKA RIalpha CNB-A turns this domain into a highly cGMP-selective domain, underlining the importance of these contacts for achieving cGMP specificity. Binding data with the generic purine nucleotide 3',5'-cyclic inosine monophosphate (cIMP) reveal that introduced arginine residues interact with the position 6 oxygen of the nucleobase. Co-crystal structures of an isolated CNB-B G316R/A336T double mutant with either cAMP or cGMP reveal that the introduced threonine and arginine residues maintain their conserved contacts as seen in PKG I CNB-B. These results improve our understanding of cyclic nucleotide binding and the molecular basis of cyclic nucleotide specificity.
Mutations of PKA cyclic nucleotide-binding domains reveal novel aspects of cyclic nucleotide selectivity.,Lorenz R, Moon EW, Kim JJ, Schmidt SH, Sankaran B, Pavlidis IV, Kim C, Herberg FW Biochem J. 2017 Jul 6;474(14):2389-2403. doi: 10.1042/BCJ20160969. PMID:28583991[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Glesne D, Huberman E. Smad6 is a protein kinase X phosphorylation substrate and is required for HL-60 cell differentiation. Oncogene. 2006 Jul 6;25(29):4086-98. Epub 2006 Feb 20. PMID:16491121 doi:http://dx.doi.org/1209436
- ↑ Santos NC, Kim KH. Activity of retinoic acid receptor-alpha is directly regulated at its protein kinase A sites in response to follicle-stimulating hormone signaling. Endocrinology. 2010 May;151(5):2361-72. doi: 10.1210/en.2009-1338. Epub 2010 Mar , 9. PMID:20215566 doi:10.1210/en.2009-1338
- ↑ Rhayem Y, Le Stunff C, Abdel Khalek W, Auzan C, Bertherat J, Linglart A, Couvineau A, Silve C, Clauser E. Functional Characterization of PRKAR1A Mutations Reveals a Unique Molecular Mechanism Causing Acrodysostosis but Multiple Mechanisms Causing Carney Complex. J Biol Chem. 2015 Nov 13;290(46):27816-28. doi: 10.1074/jbc.M115.656553. Epub, 2015 Sep 24. PMID:26405036 doi:http://dx.doi.org/10.1074/jbc.M115.656553
- ↑ Lorenz R, Moon EW, Kim JJ, Schmidt SH, Sankaran B, Pavlidis IV, Kim C, Herberg FW. Mutations of PKA cyclic nucleotide-binding domains reveal novel aspects of cyclic nucleotide selectivity. Biochem J. 2017 Jul 6;474(14):2389-2403. doi: 10.1042/BCJ20160969. PMID:28583991 doi:http://dx.doi.org/10.1042/BCJ20160969
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