1A7F

INSULIN MUTANT B16 GLU, B24 GLY, DES-B30, NMR, 20 STRUCTURES

1A7F の概要

• エントリーDOI: 10.2210/pdb1a7f/pdb
• 分子名称: INSULIN (2 entities in total)
• 機能のキーワード: hormone, human insulin mutant, monomer, neutral ph
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 5592.36

構造登録者

Ludvigsen, S.,Kaarsholm, N.C. (登録日: 1998-03-12, 公開日: 1998-07-15, 最終更新日: 2024-10-30)

主引用文献

Ludvigsen, S.,Olsen, H.B.,Kaarsholm, N.C.
A structural switch in a mutant insulin exposes key residues for receptor binding.
J.Mol.Biol., 279:1-7, 1998

PubMed Abstract: Despite years of effort to clarify the structural basis of insulin receptor binding no clear consensus has emerged. It is generally believed that insulin receptor binding is accompanied by some degree of conformational change in the carboxy-terminal of the insulin B-chain. In particular, while most substitutions for PheB24 lead to inactive species, glycine or D-amino acids are well tolerated in this position. Here we assess the conformation change by solving the solution structure of the biologically active (GluB16, GlyB24, desB30)-insulin mutant. The structure in aqueous solution at pH 8 reveals a subtle, albeit well-defined rearrangement of the C-terminal decapeptide involving a perturbation of the B20-23 turn, which allows the PheB25 residue to occupy the position normally taken up by PheB24 in native insulin. The new protein surface exposed rationalizes the receptor binding properties of a series of insulin analogs. We suggest that the structural switch is forced by the structure of the underlying core of species invariant residues and that an analogous rearrangement of the C-terminal of the B-chain occurs in native insulin on binding to its receptor.

PubMed: 9636695
DOI: 10.1006/jmbi.1998.1801

実験手法

SOLUTION NMR