5UHR
Crystal structure of (Cit)LANFLV heptapeptide segment from islet amyloid polypeptide (IAPP) incorporated into a macrocyclic beta-sheet template
Summary for 5UHR
| Entry DOI | 10.2210/pdb5uhr/pdb |
| Descriptor | ORN-CIR-LEU-ALA-ASN-PHE-LEU-VAL-ORN-ILE-LYS-HAO-LYS-A8E, CHLORIDE ION (3 entities in total) |
| Functional Keywords | amyloid, diabetes, oligomer, tetramer, de novo protein |
| Biological source | Homo sapiens |
| Total number of polymer chains | 4 |
| Total formula weight | 7411.47 |
| Authors | Wang, Y.,Kreutzer, A.G.,Nowick, J.S. (deposition date: 2017-01-11, release date: 2017-07-12, Last modification date: 2023-11-15) |
| Primary citation | Wang, Y.,Kreutzer, A.G.,Truex, N.L.,Nowick, J.S. A Tetramer Derived from Islet Amyloid Polypeptide. J. Org. Chem., 82:7905-7912, 2017 Cited by PubMed Abstract: Aggregation of the islet amyloid polypeptide (IAPP) to form fibrils and oligomers is important in the progression of type 2 diabetes. This article describes X-ray crystallographic and solution-state NMR studies of peptides derived from residues 11-17 of IAPP that assemble to form tetramers. Incorporation of residues 11-17 of IAPP (RLANFLV) into a macrocyclic β-sheet peptide results in a monomeric peptide that does not self-assemble to form oligomers. Mutation of Arg to the uncharged isostere citrulline gives peptide homologues that assemble to form tetramers in both the crystal state and in aqueous solution. The tetramers consist of hydrogen-bonded dimers that sandwich together through hydrophobic interactions. The tetramers share several features with structures reported for IAPP fibrils and demonstrate the importance of hydrogen bonding and hydrophobic interactions in the oligomerization of IAPP-derived peptides. PubMed: 28661686DOI: 10.1021/acs.joc.7b01116 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.798 Å) |
Structure validation
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