2bp4

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spinqualitylabelsall models PDB ID 2bp4 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
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ZINC-BINDING DOMAIN OF ALZHEIMER'S DISEASE AMYLOID BETA-PEPTIDE IN TFE-WATER (80-20) SOLUTION

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Alzheimer disease-1, APP-related OMIM:[104760], Amyloidosis, cerebroarterial, Dutch type OMIM:[104760], Amyloidosis, cerebroarterial, Iowa type OMIM:[104760], Blood group, P system OMIM:[607922]

About this Structure

2BP4 is a Single protein structure of sequence from [1]. This structure supersedes the now removed PDB entry 1O6N. Full crystallographic information is available from OCA.

Reference

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

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