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| | ==Crystal structure of the central domain of human AKAP18 gamma/delta in complex with malonate== | | ==Crystal structure of the central domain of human AKAP18 gamma/delta in complex with malonate== |
| - | <StructureSection load='5jj2' size='340' side='right' caption='[[5jj2]], [[Resolution|resolution]] 1.25Å' scene=''> | + | <StructureSection load='5jj2' size='340' side='right'caption='[[5jj2]], [[Resolution|resolution]] 1.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5jj2]] 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=5JJ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JJ2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5jj2]] 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=5JJ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JJ2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLI:MALONATE+ION'>MLI</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]] 1.25Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AKAP7, AKAP18 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></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=5jj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jj2 OCA], [http://pdbe.org/5jj2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jj2 RCSB], [http://www.ebi.ac.uk/pdbsum/5jj2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jj2 ProSAT]</span></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=5jj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jj2 OCA], [https://pdbe.org/5jj2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jj2 RCSB], [https://www.ebi.ac.uk/pdbsum/5jj2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jj2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AKA7G_HUMAN AKA7G_HUMAN]] Probably targets cAMP-dependent protein kinase (PKA) to the cellular membrane or cytoskeletal structures. The membrane-associated form reduces epithelial sodium channel (ENaC) activity, whereas the free cytoplasmic form may negatively regulate ENaC channel feedback inhibition by intracellular sodium.<ref>PMID:10613906</ref> <ref>PMID:17244820</ref> | + | [https://www.uniprot.org/uniprot/AKA7G_HUMAN AKA7G_HUMAN] Probably targets cAMP-dependent protein kinase (PKA) to the cellular membrane or cytoskeletal structures. The membrane-associated form reduces epithelial sodium channel (ENaC) activity, whereas the free cytoplasmic form may negatively regulate ENaC channel feedback inhibition by intracellular sodium.<ref>PMID:10613906</ref> <ref>PMID:17244820</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5jj2" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5jj2" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[A-kinase anchor protein 3D structures|A-kinase anchor protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bjerregaard-Andersen, K]] | + | [[Category: Large Structures]] |
| - | [[Category: Morth, J P]] | + | [[Category: Bjerregaard-Andersen K]] |
| - | [[Category: Ostensen, E]] | + | [[Category: Morth JP]] |
| - | [[Category: Scott, J D]] | + | [[Category: Ostensen E]] |
| - | [[Category: Tasken, K]] | + | [[Category: Scott JD]] |
| - | [[Category: A-kinase anchoring]]
| + | [[Category: Tasken K]] |
| - | [[Category: Akap]]
| + | |
| - | [[Category: Central domain]]
| + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Malonate]]
| + | |
| - | [[Category: Phospoesterase]]
| + | |
| Structural highlights
Function
AKA7G_HUMAN Probably targets cAMP-dependent protein kinase (PKA) to the cellular membrane or cytoskeletal structures. The membrane-associated form reduces epithelial sodium channel (ENaC) activity, whereas the free cytoplasmic form may negatively regulate ENaC channel feedback inhibition by intracellular sodium.[1] [2]
Publication Abstract from PubMed
A-kinase anchoring proteins (AKAPs) are a family of proteins that provide spatiotemporal resolution of protein kinase A (PKA) phosphorylation. In the myocardium, PKA and AKAP18gamma/delta are found in complex with sarcoendoplasmic reticulum Ca(2+)-ATPase 2 (SERCA2) and phospholamban (PLB). This macromolecular complex provides a means by which anchored PKA can dynamically regulate cytoplasmic Ca(2+) release and re-uptake. For this reason, AKAP18gamma/delta presents an interesting drug target with therapeutic potential in cardiovascular disease. The crystal structure of the central domain of human AKAP18gamma has been determined at the atomic resolution of 1.25 A. This first structure of human AKAP18gamma is trapped in a novel conformation by a malonate molecule bridging the important R-loop with the 2H phosphoesterase motif. Although the physiological substrate of AKAP18gamma is currently unknown, a potential proton wire deep in the central binding crevice has been indentified, leading to bulk solvent below the R-loop. Malonate complexed with AKAP18gamma at atomic resolution provides an excellent starting point for structure-guided drug design.
Malonate in the nucleotide-binding site traps human AKAP18gamma/delta in a novel conformational state.,Bjerregaard-Andersen K, Ostensen E, Scott JD, Tasken K, Morth JP Acta Crystallogr F Struct Biol Commun. 2016 Aug;72(Pt 8):591-7. doi:, 10.1107/S2053230X16010189. Epub 2016 Jul 13. PMID:27487922[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Trotter KW, Fraser ID, Scott GK, Stutts MJ, Scott JD, Milgram SL. Alternative splicing regulates the subcellular localization of A-kinase anchoring protein 18 isoforms. J Cell Biol. 1999 Dec 27;147(7):1481-92. PMID:10613906
- ↑ Bengrine A, Li J, Awayda MS. The A-kinase anchoring protein 15 regulates feedback inhibition of the epithelial Na+ channel. FASEB J. 2007 Apr;21(4):1189-201. Epub 2007 Jan 23. PMID:17244820 doi:http://dx.doi.org/10.1096/fj.06-6046com
- ↑ Bjerregaard-Andersen K, Ostensen E, Scott JD, Tasken K, Morth JP. Malonate in the nucleotide-binding site traps human AKAP18gamma/delta in a novel conformational state. Acta Crystallogr F Struct Biol Commun. 2016 Aug;72(Pt 8):591-7. doi:, 10.1107/S2053230X16010189. Epub 2016 Jul 13. PMID:27487922 doi:http://dx.doi.org/10.1107/S2053230X16010189
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