1TYL

THE STRUCTURE OF A COMPLEX OF HEXAMERIC INSULIN AND 4'-HYDROXYACETANILIDE

1TYL の概要

• エントリーDOI: 10.2210/pdb1tyl/pdb
• 分子名称: INSULIN, ZINC ION, N-(4-HYDROXYPHENYL)ACETAMIDE (TYLENOL), ... (6 entities in total)
• 機能のキーワード: hormone
• 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: 4
• 化学式量合計: 11952.74

構造登録者

Smith, G.D.,Ciszak, E. (登録日: 1994-06-21, 公開日: 1994-09-30, 最終更新日: 2024-11-13)

主引用文献

Smith, G.D.,Ciszak, E.
The structure of a complex of hexameric insulin and 4'-hydroxyacetanilide.
Proc.Natl.Acad.Sci.USA, 91:8851-8855, 1994

PubMed Abstract: X-ray crystallographic studies have been carried out on human insulin crystals grown in the presence of 4'-hydroxyacetanilide (Tylenol) and show that this nontoxic phenolic derivative can induce the T-->R transition, producing a T3R3 hexamer. Two different crystals, grown under different conditions, are rhombohedral, space group R3, with cell constants a = 81.11, c = 37.97 and a = 80.88, c = 37.60 A. The T3R3 hexamer is symmetric, resulting from the presence of a crystallographic threefold axis, and the asymmetric unit consists of a TR dimer. Data to a resolution of 1.9 A were measured on a crystal from each of the two crystallizations and the structures have been refined to residuals of 0.168 and 0.173. The guest molecule is bound by the R-state monomer through the formation of two hydrogen bonds from the hydroxy group of Tylenol to the carbonyl oxygen and the nitrogen of A6 Cys and A11 Cys, respectively. Due to steric constraints of the phenolic binding site, the acetamide group of Tylenol is rotated approximately 50 degrees out of the plane of the phenyl group and the methyl group is cis; no hydrogen bonds exist between the acetamide group and the hexamer. Although the zinc ion, which is bound to the R-state trimer, has tetrahedral coordination in both structures, the T-state zinc is observed to have octahedral coordination in one structure but tetrahedral coordination in the other. The side chain of A10 Ile in the R-state monomer adopts a high-energy conformation as a result of close contact to a residue in an adjacent dimer and may explain in part the differences between therapeutic preparations of beef insulin, for which A10 is a Val residue, and human insulin.

PubMed: 8090735
DOI: 10.1073/pnas.91.19.8851

実験手法

X-RAY DIFFRACTION (1.9 Å)