8YG2
Crystal structure of amyloidogenic peptide Piv-NFGAIL-NH2 from Islet Amyloid Polypeptide
Summary for 8YG2
| Entry DOI | 10.2210/pdb8yg2/pdb |
| Descriptor | Amyloidogenic peptide from Islet Amyloid Polypeptide, FORMIC ACID (2 entities in total) |
| Functional Keywords | amyloid, casl, protein fibril |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 761.89 |
| Authors | Sawazaki, T.,Sasaki, D.,Sohma, Y. (deposition date: 2024-02-26, release date: 2024-05-08, Last modification date: 2024-11-20) |
| Primary citation | Sawazaki, T.,Sasaki, D.,Sohma, Y. Catalysis driven by an amyloid-substrate complex. Proc.Natl.Acad.Sci.USA, 121:e2314704121-e2314704121, 2024 Cited by 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: 38691589DOI: 10.1073/pnas.2314704121 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.25 Å) |
Structure validation
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