4f0z: Difference between revisions

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 ==Crystal Structure of Calcineurin in Complex with the Calcineurin-Inhibiting Domain of the African Swine Fever Virus Protein A238L==
-<StructureSection load='4f0z' size='340' side='right' caption='[[4f0z]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+<StructureSection load='4f0z' size='340' side='right'caption='[[4f0z]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4f0z]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/African_swine_fever_virus_malawi_lil_20/1 African swine fever virus malawi lil 20/1] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F0Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F0Z FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4f0z]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/African_swine_fever_virus_Malawi_LIL_20/1 African swine fever virus Malawi LIL 20/1] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F0Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F0Z FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.7&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1aui|1aui]], [[2p6b|2p6b]], [[1mf8|1mf8]], [[1tco|1tco]], [[1m63|1m63]], [[3ll8|3ll8]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPP3CA, CALNA, CNA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), PPP3R1, CNA2, CNB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), 5EL, Mal-047, Ordered Locus Name: Mal-047 ORF Name: 5EL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10500 African swine fever virus Malawi LIL 20/1])</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=4f0z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f0z OCA], [https://pdbe.org/4f0z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f0z RCSB], [https://www.ebi.ac.uk/pdbsum/4f0z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f0z ProSAT]</span></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] </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=4f0z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f0z OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4f0z RCSB], [http://www.ebi.ac.uk/pdbsum/4f0z PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PP2BA_HUMAN PP2BA_HUMAN]] Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin. Dephosphorylates DNM1L, HSPB1 and SSH1.<ref>PMID:15671020</ref> <ref>PMID:18838687</ref>  [[http://www.uniprot.org/uniprot/VF238_ASFM2 VF238_ASFM2]] Inhibits activation of the NF-kappa-B transcription factor by preventing binding of NF-kappa-B subunits RELA and NFKB3 to DNA. Inhibits also the activity of the calcium/calmodulin-regulated phosphatase calcineurin (By similarity). [[http://www.uniprot.org/uniprot/CANB1_HUMAN CANB1_HUMAN]] Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity.
+[https://www.uniprot.org/uniprot/PP2BA_HUMAN PP2BA_HUMAN] Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin. Dephosphorylates DNM1L, HSPB1 and SSH1.<ref>PMID:15671020</ref> <ref>PMID:18838687</ref>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Ser/thr phosphatases dephosphorylate their targets with high specificity, yet the structural and sequence determinants of phosphosite recognition are poorly understood. Calcineurin (CN) is a conserved Ca/calmodulin-dependent ser/thr phosphatase and the target of immunosuppressants, FK506 and cyclosporin A (CSA). To investigate CN substrate recognition we used X-ray crystallography, biochemistry, modeling, and in vivo experiments to study A238L, a viral protein inhibitor of CN. We show that A238L competitively inhibits CN by occupying a critical substrate recognition site, while leaving the catalytic center fully accessible. Critically, the 1.7 A structure of the A238L-CN complex reveals how CN recognizes residues in A238L that are analogous to a substrate motif, "LxVP." The structure enabled modeling of a peptide substrate bound to CN, which predicts substrate interactions beyond the catalytic center. Finally, this study establishes that "LxVP" sequences and immunosuppressants bind to the identical site on CN. Thus, FK506, CSA, and A238L all prevent "LxVP"-mediated substrate recognition by CN, highlighting the importance of this interaction for substrate dephosphorylation. Collectively, this work presents the first integrated structural model for substrate selection and dephosphorylation by CN and lays the groundwork for structure-based development of new CN inhibitors.
-The molecular mechanism of substrate engagement and immunosuppressant inhibition of calcineurin.,Grigoriu S, Bond R, Cossio P, Chen JA, Ly N, Hummer G, Page R, Cyert MS, Peti W PLoS Biol. 2013 Feb;11(2):e1001492. doi: 10.1371/journal.pbio.1001492. Epub 2013 , Feb 26. PMID:23468591<ref>PMID:23468591</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+==See Also==
-</div>
+*[[Calcineurin 3D structures|Calcineurin 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: African swine fever virus malawi lil 20/1]]
+[[Category: African swine fever virus Malawi LIL 20/1]]
 [[Category: Homo sapiens]]
-[[Category: Phosphoprotein phosphatase]]
+[[Category: Large Structures]]
-[[Category: Grigoriu, S]]
+[[Category: Grigoriu S]]
-[[Category: Page, R]]
+[[Category: Page R]]
-[[Category: Peti, W]]
+[[Category: Peti W]]
-[[Category: Calcineurin inhibition]]
-[[Category: Calcium signaling]]
-[[Category: Calmodulin]]
-[[Category: Ef-hand]]
-[[Category: Heart]]
-[[Category: Hydrolase-protein binding complex]]
-[[Category: Ion channel]]
-[[Category: Lxvp]]
-[[Category: Nfat]]
-[[Category: Nucleus]]
-[[Category: Phosphatase]]
-[[Category: Pxixit]]
-[[Category: Rcan]]
-[[Category: Skeletal muscle]]
-[[Category: T-cell activation]]
-[[Category: Transcription regulation]]