5AZZ

Crystal structure of seleno-insulin

Summary for 5AZZ

• Entry DOI: 10.2210/pdb5azz/pdb
• Descriptor: Insulin A chain, Insulin B chain (3 entities in total)
• Functional Keywords: selenocysteine, insulin, hormone
• Biological source: Bos taurus (Bovine); More
• Cellular location: Secreted: P01317 P01317
• Total number of polymer chains: 2
• Total formula weight: 6099.75

Authors

Watanabe, S.,Okumura, M.,Arai, K.,Takei, T.,Asahina, Y.,Hojo, H.,Iwaoka, M.,Inaba, K. (deposition date: 2015-10-23, release date: 2017-05-03, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.45 Å)