8YG2

Crystal structure of amyloidogenic peptide Piv-NFGAIL-NH2 from Islet Amyloid Polypeptide

8YG2 の概要

• エントリーDOI: 10.2210/pdb8yg2/pdb
• 分子名称: Amyloidogenic peptide from Islet Amyloid Polypeptide, FORMIC ACID (2 entities in total)
• 機能のキーワード: amyloid, casl, protein fibril
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 761.89

構造登録者

Sawazaki, T.,Sasaki, D.,Sohma, Y. (登録日: 2024-02-26, 公開日: 2024-05-08, 最終更新日: 2024-11-20)

主引用文献

Sawazaki, T.,Sasaki, D.,Sohma, Y.
Catalysis driven by an amyloid-substrate complex.
Proc.Natl.Acad.Sci.USA, 121:e2314704121-e2314704121, 2024

PubMed Abstract: Amine modification through nucleophilic attack of the amine functionality is a very common chemical transformation. Under biorelevant conditions using acidic-to-neutral pH buffer, however, the nucleophilic reaction of alkyl amines (pKa ≈ 10) is not facile due to the generation of ammonium ions lacking nucleophilicity. Here, we disclose a unique molecular transformation system, atalysis driven by myloid-ubstrate compex (CASL), that promotes amine modifications in acidic buffer. Ammonium ions attached to molecules with amyloid-binding capability were activated through deprotonation due to the close proximity to the amyloid catalyst formed by Ac-Asn-Phe-Gly-Ala-Ile-Leu-NH (), derived from islet amyloid polypeptide (IAPP). Under the CASL conditions, alkyl amines underwent various modifications, i.e., acylation, arylation, cyclization, and alkylation, in acidic buffer. Crystallographic analysis and chemical modification studies of the amyloid catalysts suggested that the carbonyl oxygen of the Phe-Gly amide bond of plays a key role in activating the substrate amine by forming a hydrogen bond. Using CASL, selective conversion of substrates possessing equivalently reactive amine functionalities was achieved in catalytic reactions using amyloids. CASL provides a unique method for applying nucleophilic conversion reactions of amines in diverse fields of chemistry and biology.

PubMed: 38691589
DOI: 10.1073/pnas.2314704121

実験手法

X-RAY DIFFRACTION (1.25 Å)