1HIS

Structure and dynamics of des-pentapeptide-insulin in solution: the molten-globule hypothesis.

1HIS の概要

• エントリーDOI: 10.2210/pdb1his/pdb
• 分子名称: INSULIN (2 entities in total)
• 機能のキーワード: hormone
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 5225.98

構造登録者

Hua, Q.X.,Kochoyan, M.,Weiss, M.A. (登録日: 1992-02-28, 公開日: 1994-01-31, 最終更新日: 2024-11-20)

主引用文献

Hua, Q.X.,Kochoyan, M.,Weiss, M.A.
Structure and dynamics of des-pentapeptide-insulin in solution: the molten-globule hypothesis.
Proc.Natl.Acad.Sci.USA, 89:2379-2383, 1992

PubMed Abstract: Structures of insulin in different crystal forms exhibit significant local and nonlocal differences, including correlated displacement of elements of secondary structure. Here we describe the solution structure and dynamics of a monomeric insulin analogue, des-pentapeptide-(B26-B30)-insulin (DPI), as determined by two-dimensional NMR spectroscopy and distance geometry/restrained molecular dynamics (DG/RMD). Although the solution structure of DPI exhibits a general similarity to its crystal structure, individual DG/RMD structures in the NMR ensemble differ by rigid-body displacements of alpha-helices that span the range of different crystal forms. These results suggest that DPI exists as a partially folded state formed by coalescence of distinct alpha-helix-associated microdomains. The physical reality of this model is investigated by comparison of the observed two-dimensional nuclear Overhauser enhancement (NOE) spectroscopy (NOESY) spectrum with that predicted from crystal and DG/RMD structures. The observed NOESY spectrum contains fewer tertiary contacts than predicted by any single simulation, but it matches their shared features; such "ensemble correspondence" is likely to reflect the effect of protein dynamics on observed NOE intensities. We propose (i) that the folded state of DPI is analogous to that of a compact protein-folding intermediate rather than a conventional native state and (ii) that the molten state is the biologically active species. This proposal (the molten-globule hypothesis) leads to testable thermodynamic predictions and has general implications for protein design.

PubMed: 1549601
DOI: 10.1073/pnas.89.6.2379

実験手法

SOLUTION NMR