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5j31

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Revision as of 07:26, 10 June 2020

Crystal structure of 14-3-3zeta in complex with an alkyne cross-linked cyclic peptide derived from ExoS

Structural highlights

5j31 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.
Ligands:
NonStd Res:	,
Related:	4n7g, 4n7y, 4n84
Gene:	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

Macrocyclization can be used to constrain peptides in their bioactive conformations, thereby supporting target affinity and bioactivity. In particular, for the targeting of challenging protein-protein interactions, macrocyclic peptides have proven to be very useful. Available approaches focus on the stabilization of alpha-helices, which limits their general applicability. Here we report for the first time on the use of ring-closing alkyne metathesis for the stabilization of an irregular peptide secondary structure. A small library of alkyne-crosslinked peptides provided a number of derivatives with improved target affinity relative to the linear parent peptide. In addition, we report the crystal structure of the highest-affinity derivative in a complex with its protein target 14-3-3zeta. It can be expected that the alkyne-based macrocyclization of irregular binding epitopes should give rise to new scaffolds suitable for targeting of currently intractable proteins.

Constraining an Irregular Peptide Secondary Structure through Ring-Closing Alkyne Metathesis.,Cromm PM, Wallraven K, Glas A, Bier D, Furstner A, Ottmann C, Grossmann TN Chembiochem. 2016 Sep 6. doi: 10.1002/cbic.201600362. PMID:27596722^[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
↑ Cromm PM, Wallraven K, Glas A, Bier D, Furstner A, Ottmann C, Grossmann TN. Constraining an Irregular Peptide Secondary Structure through Ring-Closing Alkyne Metathesis. Chembiochem. 2016 Sep 6. doi: 10.1002/cbic.201600362. PMID:27596722 doi:http://dx.doi.org/10.1002/cbic.201600362

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/5j31"

@@ Line 1: / Line 1: @@
 ==Crystal structure of 14-3-3zeta in complex with an alkyne cross-linked cyclic peptide derived from ExoS==
-<StructureSection load='5j31' size='340' side='right' caption='[[5j31]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='5j31' size='340' side='right'caption='[[5j31]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5j31]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J31 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5J31 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5j31]] is a 4 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=5J31 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5J31 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEZ:BENZOIC+ACID'>BEZ</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEZ:BENZOIC+ACID'>BEZ</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene>, <scene name='pdbligand=ZS8:(2S)-2-AMINO-2-METHYLDEC-8-YNOIC+ACID'>ZS8</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4n7g|4n7g]], [[4n7y|4n7y]], [[4n84|4n84]]</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=5j31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j31 OCA], [http://pdbe.org/5j31 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j31 RCSB], [http://www.ebi.ac.uk/pdbsum/5j31 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j31 ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">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://proteopedia.org/fgij/fg.htm?mol=5j31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j31 OCA], [http://pdbe.org/5j31 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j31 RCSB], [http://www.ebi.ac.uk/pdbsum/5j31 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j31 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 20: / Line 21: @@
 </div>
 <div class="pdbe-citations 5j31" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Bier, D]]
 [[Category: Cromm, P]]

5j31

From Proteopedia

Revision as of 07:26, 10 June 2020

Crystal structure of 14-3-3zeta in complex with an alkyne cross-linked cyclic peptide derived from ExoS

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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