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4f0z

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Revision as of 19:43, 4 August 2016

Crystal Structure of Calcineurin in Complex with the Calcineurin-Inhibiting Domain of the African Swine Fever Virus Protein A238L

Structural highlights

4f0z is a 3 chain structure with sequence from Asfm2 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1aui, 2p6b, 1mf8, 1tco, 1m63, 3ll8
Gene:	PPP3CA, CALNA, CNA (HUMAN), PPP3R1, CNA2, CNB (HUMAN), 5EL, Mal-047, Ordered Locus Name: Mal-047 ORF Name: 5EL (ASFM2)
Activity:	Phosphoprotein phosphatase, with EC number 3.1.3.16
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] [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). [CANB1_HUMAN] Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity.

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wang Y, Shibasaki F, Mizuno K. Calcium signal-induced cofilin dephosphorylation is mediated by Slingshot via calcineurin. J Biol Chem. 2005 Apr 1;280(13):12683-9. Epub 2005 Jan 24. PMID:15671020 doi:M411494200
↑ Cereghetti GM, Stangherlin A, Martins de Brito O, Chang CR, Blackstone C, Bernardi P, Scorrano L. Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15803-8. doi:, 10.1073/pnas.0808249105. Epub 2008 Oct 6. PMID:18838687 doi:10.1073/pnas.0808249105
↑ Grigoriu S, Bond R, Cossio P, Chen JA, Ly N, Hummer G, Page R, Cyert MS, Peti W. The molecular mechanism of substrate engagement and immunosuppressant inhibition of calcineurin. PLoS Biol. 2013 Feb;11(2):e1001492. doi: 10.1371/journal.pbio.1001492. Epub 2013 , Feb 26. PMID:23468591 doi:http://dx.doi.org/10.1371/journal.pbio.1001492

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4f0z"

@@ Line 1: / Line 1: @@
 ==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=''>
 == 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 [http://en.wikipedia.org/wiki/Asfm2 Asfm2] and [http://en.wikipedia.org/wiki/Human Human]. 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>
 </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>
 <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='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='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 HUMAN]), PPP3R1, CNA2, CNB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), 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 ASFM2])</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>
+<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://pdbe.org/4f0z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4f0z RCSB], [http://www.ebi.ac.uk/pdbsum/4f0z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4f0z ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4f0z" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Calcineurin|Calcineurin]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: African swine fever virus malawi lil 20/1]]
+[[Category: Asfm2]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Phosphoprotein phosphatase]]
 [[Category: Grigoriu, S]]

4f0z

From Proteopedia

Revision as of 19:43, 4 August 2016

Crystal Structure of Calcineurin in Complex with the Calcineurin-Inhibiting Domain of the African Swine Fever Virus Protein A238L

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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