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5kjy

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Revision as of 12:18, 25 December 2019

Co-crystal structure of PKA RI alpha CNB-B mutant (G316R/A336T) with cAMP

Structural highlights

5kjy is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	5kjz, 5kjx
Gene:	PRKAR1A, PKR1, PRKAR1, TSE1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5kjy"

@@ Line 1: / Line 1: @@
 ==Co-crystal structure of PKA RI alpha CNB-B mutant (G316R/A336T) with cAMP==
-<StructureSection load='5kjy' size='340' side='right' caption='[[5kjy]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='5kjy' size='340' side='right'caption='[[5kjy]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5kjy]] is a 1 chain structure. 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 [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>
 </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>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kjz|5kjz]], [[5kjx|5kjx]]</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'>[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>
@@ Line 21: / Line 22: @@
 </div>
 <div class="pdbe-citations 5kjy" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[CAMP-dependent protein kinase 3D structures|CAMP-dependent protein kinase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Herberg, F W]]
 [[Category: Huang, G Y]]

5kjy

From Proteopedia

Revision as of 12:18, 25 December 2019

Co-crystal structure of PKA RI alpha CNB-B mutant (G316R/A336T) with cAMP

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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