5w4j: Difference between revisions
New page: '''Unreleased structure''' The entry 5w4j is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures |
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==X-ray crystallographic structure of a beta-hairpin peptide mimic. (ORN)KLV(MEA)FAE(ORN)AIIGLMV.== | |||
<StructureSection load='5w4j' size='340' side='right'caption='[[5w4j]], [[Resolution|resolution]] 2.08Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5w4j]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W4J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W4J FirstGlance]. <br> | |||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MEA:N-METHYLPHENYLALANINE'>MEA</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=5w4j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w4j OCA], [http://pdbe.org/5w4j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w4j RCSB], [http://www.ebi.ac.uk/pdbsum/5w4j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w4j ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The absence of high-resolution structures of amyloid oligomers constitutes a major gap in our understanding of amyloid diseases. A growing body of evidence indicates that oligomers of the beta-amyloid peptide Abeta are especially important in the progression of Alzheimer's disease. In many Abeta oligomers, the Abeta monomer components are thought to adopt a beta-hairpin conformation. This paper describes the design and study of a macrocyclic beta-hairpin peptide derived from Abeta16-36. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and size exclusion chromatography studies show that the Abeta16-36 beta-hairpin peptide assembles in solution to form hexamers, trimers, and dimers. X-ray crystallography reveals that the peptide assembles to form a hexamer in the crystal state and that the hexamer is composed of dimers and trimers. Lactate dehydrogenase release assays show that the oligomers formed by the Abeta16-36 beta-hairpin peptide are toxic toward neuronally derived SH-SY5Y cells. Replica-exchange molecular dynamics demonstrates that the hexamer can accommodate full-length Abeta. These findings expand our understanding of the structure, solution-phase behavior, and biological activity of Abeta oligomers and may offer insights into the molecular basis of Alzheimer's disease. | |||
A Hexamer of a Peptide Derived from Abeta16-36.,Kreutzer AG, Spencer RK, McKnelly KJ, Yoo S, Hamza IL, Salveson PJ, Nowick JS Biochemistry. 2017 Nov 14;56(45):6061-6071. doi: 10.1021/acs.biochem.7b00831., Epub 2017 Oct 27. PMID:29028351<ref>PMID:29028351</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5w4j" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Kreutzer, A G]] | |||
[[Category: Nowick, J S]] | |||
[[Category: Amyloid]] | |||
[[Category: De novo protein]] | |||
[[Category: Oligomer]] | |||
[[Category: Protein fibril]] | |||
Latest revision as of 12:46, 1 January 2020
X-ray crystallographic structure of a beta-hairpin peptide mimic. (ORN)KLV(MEA)FAE(ORN)AIIGLMV.X-ray crystallographic structure of a beta-hairpin peptide mimic. (ORN)KLV(MEA)FAE(ORN)AIIGLMV.
Structural highlights
Publication Abstract from PubMedThe absence of high-resolution structures of amyloid oligomers constitutes a major gap in our understanding of amyloid diseases. A growing body of evidence indicates that oligomers of the beta-amyloid peptide Abeta are especially important in the progression of Alzheimer's disease. In many Abeta oligomers, the Abeta monomer components are thought to adopt a beta-hairpin conformation. This paper describes the design and study of a macrocyclic beta-hairpin peptide derived from Abeta16-36. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and size exclusion chromatography studies show that the Abeta16-36 beta-hairpin peptide assembles in solution to form hexamers, trimers, and dimers. X-ray crystallography reveals that the peptide assembles to form a hexamer in the crystal state and that the hexamer is composed of dimers and trimers. Lactate dehydrogenase release assays show that the oligomers formed by the Abeta16-36 beta-hairpin peptide are toxic toward neuronally derived SH-SY5Y cells. Replica-exchange molecular dynamics demonstrates that the hexamer can accommodate full-length Abeta. These findings expand our understanding of the structure, solution-phase behavior, and biological activity of Abeta oligomers and may offer insights into the molecular basis of Alzheimer's disease. A Hexamer of a Peptide Derived from Abeta16-36.,Kreutzer AG, Spencer RK, McKnelly KJ, Yoo S, Hamza IL, Salveson PJ, Nowick JS Biochemistry. 2017 Nov 14;56(45):6061-6071. doi: 10.1021/acs.biochem.7b00831., Epub 2017 Oct 27. PMID:29028351[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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