Implications for the active form of human insulin based on the structural convergence of highly active hormone analogues

0342433 - ÚOCHB 2011 RIV US eng J - Journal Article
Jiráček, Jiří - Žáková, Lenka - Antolíková, Emília - Watson, C. J. - Turkenburg, J. P. - Dodson, G. G. - Brzozowski, A. M.
Implications for the active form of human insulin based on the structural convergence of highly active hormone analogues.
Proceedings of the National Academy of Sciences of the United States of America. Roč. 107, č. 5 (2010), s. 1966-1970. ISSN 0027-8424. E-ISSN 1091-6490
R&D Projects: GA MŠMT(CZ) LC06077; GA AV ČR KJB400550702
Institutional research plan: CEZ:AV0Z40550506
Keywords : insulin * analogue * conformation * beta-turn * N-methylation
Subject RIV: CC - Organic Chemistry
Impact factor: 9.771, year: 2010

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 (beta)-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 (beta)-turn at B24-B26 associated with a trans to cis isomerisation at the B25-B26 peptide bond.
Permanent Link: http://hdl.handle.net/11104/0185172