4n7y

From Proteopedia

(Difference between revisions)

Revision as of 11:49, 4 August 2016

Crystal structure of 14-3-3zeta in complex with a 8-carbon-linker cyclic peptide derived from ExoS

Structural highlights

4n7y is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:	,
Related:	4ihl, 3ch8, 3nkx, 4iea, 4n7g, 4n84
Gene:	NP_001129171.1, YWHAZ (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[1433Z_HUMAN] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Bioactive conformations of peptides can be stabilized by macrocyclization, resulting in increased target affinity and activity. Such macrocyclic peptides proved useful as modulators of biological functions, in particular as inhibitors of protein-protein interactions (PPI). However, most peptide-derived PPI inhibitors involve stabilized alpha-helices, leaving a large number of secondary structures unaddressed. Herein, we present a rational approach towards stabilization of an irregular peptide structure, using hydrophobic cross-links that replace residues crucially involved in target binding. The molecular basis of this interaction was elucidated by X-ray crystallography and isothermal titration calorimetry. The resulting cross-linked peptides inhibit the interaction between human adaptor protein 14-3-3 and virulence factor exoenzyme S. Taking into consideration that irregular peptide structures participate widely in PPIs, this approach provides access to novel peptide-derived inhibitors.

Constrained Peptides with Target-Adapted Cross-Links as Inhibitors of a Pathogenic Protein-Protein Interaction.,Glas A, Bier D, Hahne G, Rademacher C, Ottmann C, Grossmann TN Angew Chem Int Ed Engl. 2014 Feb 6. doi: 10.1002/anie.201310082. PMID:24504455^[6]

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

References

↑ Dubois T, Rommel C, Howell S, Steinhussen U, Soneji Y, Morrice N, Moelling K, Aitken A. 14-3-3 is phosphorylated by casein kinase I on residue 233. Phosphorylation at this site in vivo regulates Raf/14-3-3 interaction. J Biol Chem. 1997 Nov 14;272(46):28882-8. PMID:9360956
↑ Zheng W, Zhang Z, Ganguly S, Weller JL, Klein DC, Cole PA. Cellular stabilization of the melatonin rhythm enzyme induced by nonhydrolyzable phosphonate incorporation. Nat Struct Biol. 2003 Dec;10(12):1054-7. Epub 2003 Oct 26. PMID:14578935 doi:10.1038/nsb1005
↑ Tsuruta F, Sunayama J, Mori Y, Hattori S, Shimizu S, Tsujimoto Y, Yoshioka K, Masuyama N, Gotoh Y. JNK promotes Bax translocation to mitochondria through phosphorylation of 14-3-3 proteins. EMBO J. 2004 Apr 21;23(8):1889-99. Epub 2004 Apr 8. PMID:15071501 doi:10.1038/sj.emboj.7600194
↑ Ganguly S, Weller JL, Ho A, Chemineau P, Malpaux B, Klein DC. Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. Proc Natl Acad Sci U S A. 2005 Jan 25;102(4):1222-7. Epub 2005 Jan 11. PMID:15644438 doi:0406871102
↑ Gu YM, Jin YH, Choi JK, Baek KH, Yeo CY, Lee KY. Protein kinase A phosphorylates and regulates dimerization of 14-3-3 epsilon. FEBS Lett. 2006 Jan 9;580(1):305-10. Epub 2005 Dec 19. PMID:16376338 doi:S0014-5793(05)01485-7
↑ Glas A, Bier D, Hahne G, Rademacher C, Ottmann C, Grossmann TN. Constrained Peptides with Target-Adapted Cross-Links as Inhibitors of a Pathogenic Protein-Protein Interaction. Angew Chem Int Ed Engl. 2014 Feb 6. doi: 10.1002/anie.201310082. PMID:24504455 doi:http://dx.doi.org/10.1002/anie.201310082

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/4n7y"

@@ Line 1: / Line 1: @@
 ==Crystal structure of 14-3-3zeta in complex with a 8-carbon-linker cyclic peptide derived from ExoS==
 <StructureSection load='4n7y' size='340' side='right' caption='[[4n7y]], [[Resolution|resolution]] 2.16&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ihl|4ihl]], [[3ch8|3ch8]], [[3nkx|3nkx]], [[4iea|4iea]], [[4n7g|4n7g]], [[4n84|4n84]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NP_001129171.1, YWHAZ ([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=4n7y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n7y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4n7y RCSB], [http://www.ebi.ac.uk/pdbsum/4n7y 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=4n7y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n7y OCA], [http://pdbe.org/4n7y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4n7y RCSB], [http://www.ebi.ac.uk/pdbsum/4n7y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4n7y ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4n7y" style="background-color:#fffaf0;"></div>
 ==See Also==

4n7y

From Proteopedia

Revision as of 11:49, 4 August 2016

Crystal structure of 14-3-3zeta in complex with a 8-carbon-linker cyclic peptide derived from ExoS

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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