PDBsum entry 1tyl

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protein ligands metals Protein-protein interface(s) links
Hormone PDB id
Protein chains
21 a.a.
30 a.a. *
28 a.a. *
_ZN ×2
Waters ×110
* Residue conservation analysis
PDB id:
Name: Hormone
Title: The structure of a complex of hexameric insulin and 4'- hydroxyacetanilide
Structure: Insulin. Chain: a, c. Engineered: yes. Insulin. Chain: b, d. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organism_taxid: 9606
Biol. unit: Dodecamer (from PQS)
1.90Å     R-factor:   0.168    
Authors: G.D.Smith,E.Ciszak
Key ref: G.D.Smith and E.Ciszak (1994). The structure of a complex of hexameric insulin and 4'-hydroxyacetanilide. Proc Natl Acad Sci U S A, 91, 8851-8855. PubMed id: 8090735 DOI: 10.1073/pnas.91.19.8851
21-Jun-94     Release date:   30-Sep-94    
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Protein chains
Pfam   ArchSchema ?
P01308  (INS_HUMAN) -  Insulin
110 a.a.
21 a.a.
Protein chain
Pfam   ArchSchema ?
P01308  (INS_HUMAN) -  Insulin
110 a.a.
30 a.a.
Protein chain
Pfam   ArchSchema ?
P01308  (INS_HUMAN) -  Insulin
110 a.a.
28 a.a.
Key:    PfamA domain  Secondary structure

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biochemical function     hormone activity     1 term  


DOI no: 10.1073/pnas.91.19.8851 Proc Natl Acad Sci U S A 91:8851-8855 (1994)
PubMed id: 8090735  
The structure of a complex of hexameric insulin and 4'-hydroxyacetanilide.
G.D.Smith, E.Ciszak.
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.

Literature references that cite this PDB file's key reference

  PubMed id Reference
14596591 Z.L.Wan, B.Xu, Y.C.Chu, P.G.Katsoyannis, and M.A.Weiss (2003).
Crystal structure of allo-Ile(A2)-insulin, an inactive chiral analogue: implications for the mechanism of receptor binding.
  Biochemistry, 42, 12770-12783.
PDB codes: 1lw8 1pc1 1q4v
11468392 G.D.Smith, W.A.Pangborn, and R.H.Blessing (2001).
Phase changes in T(3)R(3)(f) human insulin: temperature or pressure induced?
  Acta Crystallogr D Biol Crystallogr, 57, 1091-1100.
PDB codes: 1g7a 1g7b
11092919 G.D.Smith, E.Ciszak, L.A.Magrum, W.A.Pangborn, and R.H.Blessing (2000).
R6 hexameric insulin complexed with m-cresol or resorcinol.
  Acta Crystallogr D Biol Crystallogr, 56, 1541-1548.
PDB codes: 1ev3 1ev6 1evr
11009601 H.B.Olsen, and N.C.Kaarsholm (2000).
Structural effects of protein lipidation as revealed by LysB29-myristoyl, des(B30) insulin.
  Biochemistry, 39, 11893-11900.  
10397800 H.Berchtold, and R.Hilgenfeld (1999).
Binding of phenol to R6 insulin hexamers.
  Biopolymers, 51, 165-172.  
10479347 J.P.Richards, M.P.Stickelmeyer, B.H.Frank, S.Pye, M.Barbeau, J.Radziuk, G.D.Smith, and M.R.DeFelippis (1999).
Preparation of a microcrystalline suspension formulation of Lys(B28)Pro(B29)-human insulin with ultralente properties.
  J Pharm Sci, 88, 861-867.  
9708987 J.L.Whittingham, D.J.Edwards, A.A.Antson, J.M.Clarkson, and G.G.Dodson (1998).
Interactions of phenol and m-cresol in the insulin hexamer, and their effect on the association properties of B28 pro --> Asp insulin analogues.
  Biochemistry, 37, 11516-11523.
PDB codes: 1zeg 1zeh 1zei
9153424 S.Rahuel-Clermont, C.A.French, N.C.Kaarsholm, M.F.Dunn, and C.I.Chou (1997).
Mechanisms of stabilization of the insulin hexamer through allosteric ligand interactions.
  Biochemistry, 36, 5837-5845.  
8842243 C.M.Yip, and M.D.Ward (1996).
Atomic force microscopy of insulin single crystals: direct visualization of molecules and crystal growth.
  Biophys J, 71, 1071-1078.  
  8976561 D.L.Bakaysa, J.Radziuk, H.A.Havel, M.L.Brader, S.Li, S.W.Dodd, J.M.Beals, A.H.Pekar, and D.N.Brems (1996).
Physicochemical basis for the rapid time-action of LysB28ProB29-insulin: dissociation of a protein-ligand complex.
  Protein Sci, 5, 2521-2531.  
8611526 D.T.Birnbaum, S.W.Dodd, B.E.Saxberg, A.D.Varshavsky, and J.M.Beals (1996).
Hierarchical modeling of phenolic ligand binding to 2Zn--insulin hexamers.
  Biochemistry, 35, 5366-5378.  
  8844841 G.D.Smith, E.Ciszak, and W.Pangborn (1996).
A novel complex of a phenolic derivative with insulin: structural features related to the T-->R transition.
  Protein Sci, 5, 1502-1511.
PDB code: 1ben
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