3nfl

From Proteopedia

(Difference between revisions)

Revision as of 04:07, 10 December 2016

Crystal structure of the PTPN4 PDZ domain complexed with the C-terminus of the GluN2A NMDA receptor subunit

Structural highlights

3nfl is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2vph, 2cs5, 3nfk
Gene:	PTPN4 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[NMDE1_HUMAN] Landau-Kleffner syndrome;Early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation;Continuous spikes and waves during sleep;Rolandic epilepsy;Rolandic epilepsy - speech dyspraxia. The disease is caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving GRIN2A has been found in a family with epilepsy and neurodevelopmental defects. Translocation t(16;17)(p13.2;q11.2). GRIN2A somatic mutations have been frequently found in cutaneous malignant melanoma, suggesting that the glutamate signaling pathway may play a role in the pathogenesis of melanoma.^[1] ^[2]

Function

[PTN4_HUMAN] May act at junctions between the membrane and the cytoskeleton. [NMDE1_HUMAN] NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Activation requires binding of agonist to both types of subunits.

Publication Abstract from PubMed

PTPN4, a human tyrosine phosphatase, protects cells against apoptosis. This protection could be abrogated by targeting the PDZ domain of this phosphatase with a peptide mimicking the C-terminal sequence of the G protein of an attenuated rabies virus strain. Here, we demonstrate that glioblastoma death is triggered upon intracellular delivery of peptides, either from viral origin or from known endogenous ligands of PTPN4-PDZ, such as the C terminus sequence of the glutamate receptor subunit GluN2A. The killing efficiency of peptides closely reflects their affinities for the PTPN4-PDZ. The crystal structures of two PTPN4-PDZ/peptide complexes allow us to pinpoint the main structural determinants of binding and to synthesize a peptide of high affinity for PTPN4-PDZ enhancing markedly its cell death capacity. These results allow us to propose a potential mechanism for the efficiency of peptides and provide a target and a robust framework for the design of new pro-death compounds.

Peptides targeting the PDZ domain of PTPN4 are efficient inducers of glioblastoma cell death.,Babault N, Cordier F, Lafage M, Cockburn J, Haouz A, Prehaud C, Rey FA, Delepierre M, Buc H, Lafon M, Wolff N Structure. 2011 Oct 12;19(10):1518-24. PMID:22000519^[3]

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

References

↑ Wei X, Walia V, Lin JC, Teer JK, Prickett TD, Gartner J, Davis S, Stemke-Hale K, Davies MA, Gershenwald JE, Robinson W, Robinson S, Rosenberg SA, Samuels Y. Exome sequencing identifies GRIN2A as frequently mutated in melanoma. Nat Genet. 2011 May;43(5):442-6. doi: 10.1038/ng.810. Epub 2011 Apr 15. PMID:21499247 doi:http://dx.doi.org/10.1038/ng.810
↑ D'mello SA, Flanagan JU, Green TN, Leung EY, Askarian-Amiri ME, Joseph WR, McCrystal MR, Isaacs RJ, Shaw JH, Furneaux CE, During MJ, Finlay GJ, Baguley BC, Kalev-Zylinska ML. Evidence That GRIN2A Mutations in Melanoma Correlate with Decreased Survival. Front Oncol. 2014 Jan 13;3:333. doi: 10.3389/fonc.2013.00333. eCollection 2014, Jan 13. PMID:24455489 doi:http://dx.doi.org/10.3389/fonc.2013.00333
↑ Babault N, Cordier F, Lafage M, Cockburn J, Haouz A, Prehaud C, Rey FA, Delepierre M, Buc H, Lafon M, Wolff N. Peptides targeting the PDZ domain of PTPN4 are efficient inducers of glioblastoma cell death. Structure. 2011 Oct 12;19(10):1518-24. PMID:22000519 doi:10.1016/j.str.2011.07.007

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/3nfl"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the PTPN4 PDZ domain complexed with the C-terminus of the GluN2A NMDA receptor subunit==
 <StructureSection load='3nfl' size='340' side='right' caption='[[3nfl]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3nfl]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NFL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NFL FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3nfl]] is a 8 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=3NFL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NFL FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vph|2vph]], [[2cs5|2cs5]], [[3nfk|3nfk]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPN4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPN4 ([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=3nfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nfl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3nfl RCSB], [http://www.ebi.ac.uk/pdbsum/3nfl 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=3nfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nfl OCA], [http://pdbe.org/3nfl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3nfl RCSB], [http://www.ebi.ac.uk/pdbsum/3nfl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3nfl ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ 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 3nfl" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 26: / Line 28: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Babault, N]]
 [[Category: Buc, H]]

3nfl

From Proteopedia

Revision as of 04:07, 10 December 2016

Crystal structure of the PTPN4 PDZ domain complexed with the C-terminus of the GluN2A NMDA receptor subunit

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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