1ze9: Difference between revisions
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== | ==Zinc-binding domain of Alzheimer's disease amyloid beta-peptide complexed with a zinc (II) cation== | ||
<StructureSection load='1ze9' size='340' side='right'caption='[[1ze9]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1ze9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZE9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZE9 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ze9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ze9 OCA], [https://pdbe.org/1ze9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ze9 RCSB], [https://www.ebi.ac.uk/pdbsum/1ze9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ze9 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Amyloid deposits within the cerebral tissue constitute a characteristic lesion associated with Alzheimer disease. They mainly consist of the amyloid peptide Abeta and display an abnormal content in Zn(2+) ions, together with many truncated, isomerized, and racemized forms of Abeta. The region 1-16 of Abeta can be considered the minimal zinc-binding domain and contains two aspartates subject to protein aging. The influence of zinc binding and protein aging related modifications on the conformation of this region of Abeta is of importance given the potentiality of this domain to constitute a therapeutic target, especially for immunization approaches. In this study, we determined from NMR data the solution structure of the Abeta-(1-16)-Zn(2+) complex in aqueous solution at pH 6.5. The residues His(6), His(13), and His(14) and the Glu(11) carboxylate were identified as ligands that tetrahedrally coordinate the Zn(II) cation. In vitro aging experiments on Abeta-(1-16) led to the formation of truncated and isomerized species. The major isomer generated, Abeta-(1-16)-l-iso-Asp(7), displayed a local conformational change in the His(6)-Ser(8) region but kept a zinc binding propensity via a coordination mode involving l-iso-Asp(7). These results are discussed here with regard to Abeta fibrillogenesis and the potentiality of the region 1-16 of Abeta to be used as a therapeutic target. | |||
Structural changes of region 1-16 of the Alzheimer disease amyloid beta-peptide upon zinc binding and in vitro aging.,Zirah S, Kozin SA, Mazur AK, Blond A, Cheminant M, Segalas-Milazzo I, Debey P, Rebuffat S J Biol Chem. 2006 Jan 27;281(4):2151-61. Epub 2005 Nov 21. PMID:16301322<ref>PMID:16301322</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1ze9" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Amyloid precursor protein 3D structures|Amyloid precursor protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Blond A]] | |||
[[Category: Cheminant M]] | |||
[[Category: Debey P]] | |||
[[Category: Kozin SA]] | |||
[[Category: Mazur AK]] | |||
[[Category: Rebuffat S]] | |||
[[Category: Segalas-Milazzo I]] | |||
[[Category: Zirah S]] | |||
Latest revision as of 03:44, 21 November 2024
Zinc-binding domain of Alzheimer's disease amyloid beta-peptide complexed with a zinc (II) cationZinc-binding domain of Alzheimer's disease amyloid beta-peptide complexed with a zinc (II) cation
Structural highlights
Publication Abstract from PubMedAmyloid deposits within the cerebral tissue constitute a characteristic lesion associated with Alzheimer disease. They mainly consist of the amyloid peptide Abeta and display an abnormal content in Zn(2+) ions, together with many truncated, isomerized, and racemized forms of Abeta. The region 1-16 of Abeta can be considered the minimal zinc-binding domain and contains two aspartates subject to protein aging. The influence of zinc binding and protein aging related modifications on the conformation of this region of Abeta is of importance given the potentiality of this domain to constitute a therapeutic target, especially for immunization approaches. In this study, we determined from NMR data the solution structure of the Abeta-(1-16)-Zn(2+) complex in aqueous solution at pH 6.5. The residues His(6), His(13), and His(14) and the Glu(11) carboxylate were identified as ligands that tetrahedrally coordinate the Zn(II) cation. In vitro aging experiments on Abeta-(1-16) led to the formation of truncated and isomerized species. The major isomer generated, Abeta-(1-16)-l-iso-Asp(7), displayed a local conformational change in the His(6)-Ser(8) region but kept a zinc binding propensity via a coordination mode involving l-iso-Asp(7). These results are discussed here with regard to Abeta fibrillogenesis and the potentiality of the region 1-16 of Abeta to be used as a therapeutic target. Structural changes of region 1-16 of the Alzheimer disease amyloid beta-peptide upon zinc binding and in vitro aging.,Zirah S, Kozin SA, Mazur AK, Blond A, Cheminant M, Segalas-Milazzo I, Debey P, Rebuffat S J Biol Chem. 2006 Jan 27;281(4):2151-61. Epub 2005 Nov 21. PMID:16301322[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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