1TYL

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

Summary for 1TYL

• Entry DOI: 10.2210/pdb1tyl/pdb
• Descriptor: INSULIN, ZINC ION, N-(4-HYDROXYPHENYL)ACETAMIDE (TYLENOL), ... (6 entities in total)
• Functional Keywords: hormone
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P01308 P01308
• Total number of polymer chains: 4
• Total formula weight: 11952.74

Authors

Smith, G.D.,Ciszak, E. (deposition date: 1994-06-21, release date: 1994-09-30, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)