6cg4: Difference between revisions

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-'''Unreleased structure'''
-The entry 6cg4 is ON HOLD  until Paper Publication
+==Covalently crosslinked trimer of a macrocyclic peptide derived from Abeta(17-36) - (ORN)LCVFFCED(ORN)AII(2-nitrobenzylglycine)L(ORN)V==
+<StructureSection load='6cg4' size='340' side='right' caption='[[6cg4]], [[Resolution|resolution]] 2.08&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6cg4]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CG4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CG4 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr>
+<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=EZY:'>EZY</scene>, <scene name='pdbligand=ORN:L-ORNITHINE'>ORN</scene></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=6cg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cg4 OCA], [http://pdbe.org/6cg4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cg4 RCSB], [http://www.ebi.ac.uk/pdbsum/6cg4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cg4 ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A key challenge in studying the biological and biophysical properties of amyloid-forming peptides is that they assemble to form heterogeneous mixtures of soluble oligomers and insoluble fibrils. Photolabile protecting groups have emerged as tools to control the properties of biomolecules with light. Blocking intermolecular hydrogen bonds that stabilize amyloid oligomers provides a general strategy to control the biological and biophysical properties of amyloid-forming peptides. In this paper we describe the design, synthesis, and characterization of macrocyclic beta-hairpin peptides that are derived from amyloidogenic peptides and contain the N-2-nitrobenzyl photolabile protecting group. Each peptide contains two heptapeptide segments from Abeta16-36 or Abeta17-36 constrained into beta-hairpins. The N-2-nitrobenzyl group is appended to the amide backbone of Gly33 to disrupt the oligomerization of the peptides by disrupting intermolecular hydrogen bonds. X-ray crystallography reveals that N-2-nitrobenzyl groups can either block assembly into discrete oligomers or permit formation of trimers, hexamers, and dodecamers. Photolysis of the N-2-nitrobenzyl groups with long-wave UV light unmasks the amide backbone and alters the assembly and the biological properties of the macrocyclic beta-hairpin peptides. SDS-PAGE studies show that removing the N-2-nitrobenzyl groups alters the assembly of the peptides. MTT conversion and LDH release assays show that decaging the peptides induces cytotoxicity. Circular dichroism studies and dye leakage assays with liposomes reveal that decaging modulates interactions of the peptides with lipid bilayers. Collectively, these studies demonstrate that incorporating N-2-nitrobenzyl groups into macrocyclic beta-hairpin peptides provides a new strategy to probe the structures and the biological properties of amyloid oligomers.
-Authors: Salveson, P.J., Nowick, J.S.
+Controlling the Oligomerization State of Abeta-Derived Peptides with Light.,Salveson PJ, Haerianardakani S, Thuy-Boun A, Kreutzer AG, Nowick JS J Am Chem Soc. 2018 May 2;140(17):5842-5852. doi: 10.1021/jacs.8b02658. Epub 2018, Apr 20. PMID:29627987<ref>PMID:29627987</ref>
-Description: Covalently crosslinked trimer of a macrocyclic peptide derived from Abeta(17-36) -(ORN)LCVFFCED(ORN)AII(2-nitrobenzylglycine)L(ORN)V
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Salveson, P.J]]
+<div class="pdbe-citations 6cg4" style="background-color:#fffaf0;"></div>
-[[Category: Nowick, J.S]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Nowick, J S]]
+[[Category: Salveson, P J]]
+[[Category: Abeta]]
+[[Category: Alzheimer's disease]]
+[[Category: Amyloid]]
+[[Category: Neuropeptide]]
+[[Category: Oligomer]]