5AZZ

Crystal structure of seleno-insulin

5AZZ の概要

• エントリーDOI: 10.2210/pdb5azz/pdb
• 分子名称: Insulin A chain, Insulin B chain (3 entities in total)
• 機能のキーワード: selenocysteine, insulin, hormone
• 由来する生物種: Bos taurus (Bovine); 詳細
• 細胞内の位置: Secreted: P01317 P01317
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 6099.75

構造登録者

Watanabe, S.,Okumura, M.,Arai, K.,Takei, T.,Asahina, Y.,Hojo, H.,Iwaoka, M.,Inaba, K. (登録日: 2015-10-23, 公開日: 2017-05-03, 最終更新日: 2024-11-13)

主引用文献

Arai, K.,Takei, T.,Okumura, M.,Watanabe, S.,Amagai, Y.,Asahina, Y.,Moroder, L.,Hojo, H.,Inaba, K.,Iwaoka, M.
Preparation of Selenoinsulin as a Long-Lasting Insulin Analogue.
Angew. Chem. Int. Ed. Engl., 56:5522-5526, 2017

PubMed Abstract: Synthetic insulin analogues with a long lifetime are current drug targets for the therapy of diabetic patients. The replacement of the interchain disulfide with a diselenide bridge, which is more resistant to reduction and internal bond rotation, can enhance the lifetime of insulin in the presence of the insulin-degrading enzyme (IDE) without impairing the hormonal function. The [C7U ,C7U ] variant of bovine pancreatic insulin (BPIns) was successfully prepared by using two selenocysteine peptides (i.e., the C7U analogues of A- and B-chains, respectively). In a buffer solution at pH 10 they spontaneously assembled under thermodynamic control to the correct insulin fold. The selenoinsulin (Se-Ins) exhibited a bioactivity comparable to that of BPIns. Interestingly, degradation of Se-Ins with IDE was significantly decelerated (τ ≈8 h vs. ≈1 h for BPIns). The lifetime enhancement could be due to both the intrinsic stability of the diselenide bond and local conformational changes induced by the substitution.

PubMed: 28394477
DOI: 10.1002/anie.201701654

実験手法

X-RAY DIFFRACTION (1.45 Å)