科学家发现了一种让胰岛素活化必需的关键结构变化，这可能带来改良的糖尿病疗法。胰岛素调控血糖浓度，而且对脂肪和蛋白质代谢具有广泛影响；这种小激素的浓度减少或细胞对其存在的不敏感通常会导致糖尿病——全球将近3%的人口受该病的影响。胰岛素由AB两个肽链组成，由分子内键将其稳定。
Andrzej Brzozowski及其同事设计并分析了具有高度活性的胰岛素相似体的结构，从而确定这种激素在它的受体上的活化形态的准确结构，这在很大程度上是未知的。这组科学家发现， 缩短这种蛋白质B链上的一种蛋白质残基会导致胰岛素从活化转向不活化。这组科学家报告说，这种蛋白质改变带来的构象变化显示了去掉的氨基酸涉及了胰岛素与其受体的结合。这组作者说，这些氨基酸可能为实验方法提供结构细节，从而设计出有效治疗糖尿病的配合物。（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS January 25, 2010, doi: 10.1073/pnas.0911785107
Implications for the active form of human insulin based on the structural convergence of highly active hormone analogues
Ji?í Jirá?eka, Lenka ?ákováa, Emília Antolíkováa, Christopher J. Watsonb, Johan P. Turkenburgb, Guy G. Dodsonb, and Andrzej M. Brzozowskib,1
aInstitute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nám. 2, 166 10 Prague 6, Czech Republic and
bYork Structural Biology Laboratory, Department of Chemistry, The University of York, Heslington, York, YO10 5YW, United Kingdom
Insulin is a key protein hormone that regulates blood glucose levels and, thus, has widespread impact on lipid and protein metabolism. Insulin action is manifested through binding of its monomeric form to the Insulin Receptor (IR). At present, however, our knowledge about the structural behavior of insulin is based upon inactive, multimeric, and storage-like states. The active monomeric structure, when in complex with the receptor, must be different as the residues crucial for the interactions are buried within the multimeric forms. Although the exact nature of the insulin’s induced-fit is unknown, there is strong evidence that the C-terminal part of the B-chain is a dynamic element in insulin activation and receptor binding. Here, we present the design and analysis of highly active (200–500%) insulin analogues that are truncated at residue 26 of the B-chain (B26). They show a structural convergence in the form of a new β-turn at B24-B26. We propose that the key element in insulin’s transition, from an inactive to an active state, may be the formation of the β-turn at B24-B26 associated with a trans to cis isomerisation at the B25-B26 peptide bond. Here, this turn is achieved with N-methylated L-amino acids adjacent to the trans to cis switch at the B25-B26 peptide bond or by the insertion of certain D-amino acids at B26. The resultant conformational changes unmask previously buried amino acids that are implicated in IR binding and provide structural details for new approaches in rational design of ligands effective in combating diabetes.
