5LFY

Zinc bound dimer of the fragment of human amyloid-beta peptide with Alzheimer's disease pathogenic Taiwanese mutation D7H

5LFY の概要

• エントリーDOI: 10.2210/pdb5lfy/pdb
• NMR情報: BMRB: 34019
• 分子名称: Amyloid beta A4 protein, ZINC ION (2 entities in total)
• 機能のキーワード: alzheimer's disease, amyloid-beta peptide, zinc complex, zinc-bound dimer, structural protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 2569.35

構造登録者

Polshakov, V.I.,Mantsyzov, A.B.,Kozin, S.A. (登録日: 2016-07-05, 公開日: 2017-08-23, 最終更新日: 2024-11-13)

主引用文献

Polshakov, V.I.,Mantsyzov, A.B.,Kozin, S.A.,Adzhubei, A.A.,Zhokhov, S.S.,van Beek, W.,Kulikova, A.A.,Indeykina, M.I.,Mitkevich, V.A.,Makarov, A.A.
A Binuclear Zinc Interaction Fold Discovered in the Homodimer of Alzheimer's Amyloid-beta Fragment with Taiwanese Mutation D7H.
Angew. Chem. Int. Ed. Engl., 56:11734-11739, 2017

PubMed Abstract: Zinc-induced oligomerization of amyloid-β peptide (Aβ) produces potentially pathogenic agents of Alzheimer's disease. Mutations and modifications in the metal binding domain 1-16 of Aβ peptide crucially affect its zinc-induced oligomerization by changing intermolecular zinc mediated interface. The 3D structure of this interface appearing in a range of Aβ species is a prospective drug target for disease modifying therapy. Using NMR spectroscopy, EXAFS spectroscopy, mass spectrometry, and isothermal titration calorimetry the interaction of zinc ions with Aβ fragments 1-7 and 1-10 carrying familial Taiwanese mutation D7H was studied. Zinc ions induce formation of a stable homodimer formed by the two peptide chains fastened by two zinc ions and stacking interactions of imidazole rings. A binuclear zinc interaction fold in the dimer structure was discovered. It can be used for designing zinc-regulated proteins and zinc-mediated self-assembling peptides.

PubMed: 28570778
DOI: 10.1002/anie.201704615

実験手法

SOLUTION NMR