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6fnc

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Mono- and bivalent 14-3-3 inhibitors for characterizing supramolecular lysine-PEG interactions in proteins

Structural highlights

6fnc is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
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

Previous studies have indicated the presence of defined interactions between oligo or poly(ethylene glycol) (OEG or PEG) and lysine residues. In these interactions, the OEG or PEG residues 'wrap around' the lysine amino group, thereby enabling complexation of the amino group by the ether oxygen residues. The resulting biochemical binding affinity and thus biological relevance of this supramolecular interaction however remains unclear so far. Here, we report that OEG-containing phosphophenol ether inhibitors of 14-3-3 proteins also display such a 'lysine-wrapping' binding mode. For better investigating the biochemical relevance of this binding mode, we made use of the dimeric nature of 14-3-3 proteins and designed as well as synthesized a set of bivalent 14-3-3 inhibitors for biochemical and X-ray crystallography-based structural studies. We found that all synthesized derivatives adapted the 'lysine-wrapping' binding mode in the crystal structures; in solution, a different binding mode is however observed, most probably as the 'lysine-wrapping' binding mode turned out to be a rather weak interaction. Accordingly, our studies demonstrate that structural studies of OEG-lysine interactions are difficult to interpret and their presence in structural studies may not automatically be correlated with a relevant interaction also in solution but requires further biochemical studies.

Mono- and bivalent 14-3-3 inhibitors for characterizing supramolecular 'lysine wrapping' of oligoethylene glycol (OEG) moieties in proteins.,Yilmaz E, Bier D, Guillory X, Briels J, Ruiz-Blanco Y, Sanchez-Garcia E, Ottmann C, Kaiser M Chemistry. 2018 Jun 20. doi: 10.1002/chem.201801074. PMID:29924885^[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
↑ Yilmaz E, Bier D, Guillory X, Briels J, Ruiz-Blanco Y, Sanchez-Garcia E, Ottmann C, Kaiser M. Mono- and bivalent 14-3-3 inhibitors for characterizing supramolecular 'lysine wrapping' of oligoethylene glycol (OEG) moieties in proteins. Chemistry. 2018 Jun 20. doi: 10.1002/chem.201801074. PMID:29924885 doi:http://dx.doi.org/10.1002/chem.201801074

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6fnc"

@@ Line 3: / Line 3: @@
 <StructureSection load='6fnc' size='340' side='right' caption='[[6fnc]], [[Resolution|resolution]] 2.12&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6fnc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FNC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FNC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6fnc]] is a 2 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=6FNC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FNC 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>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DWK:[2-[2-oxidanylidene-2-[[3-[3-[2-[2-[3-[[4-[2-(2-phosphonophenoxy)ethanoylamino]phenyl]carbonylamino]propoxy]ethoxy]ethoxy]propylcarbamoyl]phenyl]amino]ethoxy]phenyl]phosphonic+acid'>DWK</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6fnc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fnc OCA], [http://pdbe.org/6fnc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fnc RCSB], [http://www.ebi.ac.uk/pdbsum/6fnc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fnc ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Bier, D]]
 [[Category: Ottann, C]]

6fnc

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Current revision

Mono- and bivalent 14-3-3 inhibitors for characterizing supramolecular lysine-PEG interactions in proteins

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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