2JMN

NMR structure of human insulin mutant His-B10-Asp, Pro-B28-Lys, Lys-B29-Pro, 20 structures

「1LNP」から置き換えられました 「1VKS」から置き換えられました

2JMN の概要

• エントリーDOI: 10.2210/pdb2jmn/pdb
• 関連するPDBエントリー: 2H67
• 分子名称: Insulin A chain, Insulin B chain (2 entities in total)
• 機能のキーワード: hormone, human insulin, mutant, hormone-growth factor complex, hormone/growth factor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted: P01308 P01308
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 5794.59

構造登録者

Hua, Q.X.,Hu, S.Q.,Frank, B.H.,Jia, W.H.,Chu, Y.C.,Wang, S.H.,Burke, G.T.,Katsoyannis, P.G.,Weiss, M.A. (登録日: 2006-11-21, 公開日: 2006-12-05, 最終更新日: 2024-10-30)

主引用文献

Hua, Q.X.,Hu, S.Q.,Frank, B.H.,Jia, W.,Chu, Y.C.,Wang, S.H.,Burke, G.T.,Katsoyannis, P.G.,Weiss, M.A.
Mapping the functional surface of insulin by design: structure and function of a novel A-chain analogue.
J.Mol.Biol., 264:390-403, 1996

PubMed Abstract: Functional surfaces of a protein are often mapped by combination of X-ray crystallography and mutagenesis. Such studies of insulin have yielded paradoxical results, suggesting that the native state is inactive and reorganizes on receptor binding. Of particular interest is the N-terminal alpha-helix of the A-chain. Does this segment function as an alpha-helix or reorganize as recently proposed in a prohormone-convertase complex? To correlate structure and function, we describe a mapping strategy based on protein design. The solution structure of an engineered monomer ([AspB10, LysB28, ProB29]-human insulin) is determined at neutral pH as a template for synthesis of a novel A-chain analogue. Designed by analogy to a protein-folding intermediate, the analogue lacks the A6-A11 disulphide bridge; the cysteine residues are replaced by serine. Its solution structure is remarkable for segmental unfolding of the N-terminal A-chain alpha-helix (A1 to A8) in an otherwise native subdomain. The structure demonstrates that the overall orientation of the A and B chains is consistent with reorganization of the A-chain's N-terminal segment. Nevertheless, the analogue's low biological activity suggests that this segment, a site of clinical mutation causing diabetes mellitus, functions as a preformed recognition alpha-helix.

PubMed: 8951384
DOI: 10.1006/jmbi.1996.0648

実験手法

SOLUTION NMR