Loading
PDBj
MenuPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDB
RCSB PDBPDBeBMRBAdv. SearchSearch help

1TYM

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

Summary for 1TYM
Entry DOI10.2210/pdb1tym/pdb
DescriptorINSULIN, ZINC ION, N-(4-HYDROXYPHENYL)ACETAMIDE (TYLENOL), ... (6 entities in total)
Functional Keywordshormone
Biological sourceHomo sapiens (human)
More
Cellular locationSecreted: P01308 P01308
Total number of polymer chains4
Total formula weight11952.74
Authors
Smith, G.D.,Ciszak, E. (deposition date: 1994-06-21, release date: 1994-09-30, Last modification date: 2024-10-30)
Primary citationSmith, G.D.,Ciszak, E.
The structure of a complex of hexameric insulin and 4'-hydroxyacetanilide.
Proc.Natl.Acad.Sci.USA, 91:8851-8855, 1994
Cited by
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
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.9 Å)
Structure validation

227561

PDB entries from 2024-11-20

PDB statisticsPDBj update infoContact PDBjnumon