PDBsum entry 1aiy

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Hormone PDB id
Protein chains
(+ 0 more) 21 a.a.
(+ 0 more) 30 a.a. *
IPH ×6
_ZN ×2
Waters ×6
* Residue conservation analysis
PDB id:
Name: Hormone
Title: R6 human insulin hexamer (symmetric), nmr, 10 structures
Structure: R6 insulin hexamer. Chain: a, c, e, g, i, k. R6 insulin hexamer. Chain: b, d, f, h, j, l
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: pancreas. Organ: pancreas
NMR struc: 10 models
Authors: X.Chang,A.M.M.Jorgensen,P.Bardrum,J.J.Led
Key ref:
X.Chang et al. (1997). Solution structures of the R6 human insulin hexamer,. Biochemistry, 36, 9409-9422. PubMed id: 9235985 DOI: 10.1021/bi9631069
30-Apr-97     Release date:   12-Nov-97    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P01308  (INS_HUMAN) -  Insulin
110 a.a.
21 a.a.
Protein chains
Pfam   ArchSchema ?
P01308  (INS_HUMAN) -  Insulin
110 a.a.
30 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: 10.1021/bi9631069 Biochemistry 36:9409-9422 (1997)
PubMed id: 9235985  
Solution structures of the R6 human insulin hexamer,.
X.Chang, A.M.Jorgensen, P.Bardrum, J.J.Led.
The three-dimensional solution structure of the phenol-stabilized 36 kDa R6 insulin hexamer was determined by NMR spectroscopy and restrained molecular dynamics. The hexamer structures were derived using a stepwise procedure. Initially, 60 monomers were obtained by distance geometry from 665 NOE-derived distance restraints and three disulfide bridges. Subsequently, the hexamer structures were calculated by simulated annealing, using 30 hexamers constructed from the best 36 monomer structures as the starting models. The NMR data show that the aromatic ring of residue Phe(B25) can take two different orientations in the solution hexamer: one in which it points inward (molecule 1, about 90%) and one in which it points outward from the surface of the monomer (molecule 2, about 10%). Therefore, two hexamer structures were calculated: a symmetric hexamer consisting of six molecule 1 monomers and a nonsymmetric hexamer consisting of five molecule 1 monomers and one molecule 2 monomer. For each of the six monomers, the restraints used in the calculations of the hexamer structures include, in addition to the intramonomeric restraints, 25 NOEs between insulin and phenol, 23 NOEs and two hydrogen bonds across the dimer interface, nine NOEs across the trimer interface, and five intramonomeric or two intermonomeric NOEs, respectively, specifying the different orientations of the Phe(B25) ring. The coordination of the two Zn atoms was defined by eight distance restraints. Thus, a total of 4394 and 4391 distance restraints, respectively, were used in the two hexamer calculations. The NOE restraints were classified in an iterative process as intra- or intermonomeric on the basis of their consistency or inconsistency with the structure of the monomer. The assignment of the dimer- and trimer-specific NOEs was made using the crystal structure of the R6 hexamer as the starting model. For both solution hexamers, the average backbone rms deviation is 0.81 A, if the less well-defined N- and C-terminal residues are excluded. The corresponding rms deviations for all heavy atoms are 1.17 and 1.19 A for the nonsymmetric and symmetric hexamer, respectively. The overall solution structure of the R6 insulin hexamer is compact, rigid, and symmetric and resembles the corresponding crystal structure. However, the extension of the B-chain alpha-helix, which characterizes the R state, is shorter in the solution structure than in the crystal structure. Also, the study shows that the orientation of the Phe(B25) ring has no effect on the structure of the rest of the molecule, within the uncertainty of the structure determination. The importance of these findings for the current model for the insulin-receptor interaction is discussed.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20697659 A.C.Welinder, J.Zhang, D.B.Steensgaard, and J.Ulstrup (2010).
Adsorption of human insulin on single-crystal gold surfaces investigated by in situ scanning tunnelling microscopy and electrochemistry.
  Phys Chem Chem Phys, 12, 9999.  
21072358 H.Sakurai, A.Katoh, T.Kiss, T.Jakusch, and M.Hattori (2010).
Metallo-allixinate complexes with anti-diabetic and anti-metabolic syndrome activities.
  Metallomics, 2, 670-682.  
20336256 Z.Ganim, K.C.Jones, and A.Tokmakoff (2010).
Insulin dimer dissociation and unfolding revealed by amide I two-dimensional infrared spectroscopy.
  Phys Chem Chem Phys, 12, 3579-3588.  
19101970 A.K.Petrus, D.G.Allis, R.P.Smith, T.J.Fairchild, and R.P.Doyle (2009).
Exploring the implications of vitamin B12 conjugation to insulin on insulin receptor binding.
  ChemMedChem, 4, 421-426.  
  19130513 D.H.Zhou, G.Shah, C.Mullen, D.Sandoz, and C.M.Rienstra (2009).
Proton-detected solid-state NMR spectroscopy of natural-abundance peptide and protein pharmaceuticals.
  Angew Chem Int Ed Engl, 48, 1253-1256.  
19145608 D.Keidel, M.Bonaccio, N.Ghaderi, D.Niks, D.Borchardt, and M.F.Dunn (2009).
1H[19F] NOE NMR structural signatures of the insulin R6 hexamer: evidence of a capped HisB10 site in aryl- and arylacryloyl-carboxylate complexes.
  Chembiochem, 10, 450-453.  
19340886 M.J.Maltesen, S.Bjerregaard, L.Hovgaard, S.Havelund, and M.van de Weert (2009).
Analysis of insulin allostery in solution and solid state with FTIR.
  J Pharm Sci, 98, 3265-3277.  
19086273 E.E.Büllesbach, M.A.Hass, M.R.Jensen, D.F.Hansen, S.M.Kristensen, C.Schwabe, and J.J.Led (2008).
Solution structure of a conformationally restricted fully active derivative of the human relaxin-like factor.
  Biochemistry, 47, 13308-13317.
PDB codes: 2k6t 2k6u
18676643 H.Vashisth, and C.F.Abrams (2008).
Ligand escape pathways and (un)binding free energy calculations for the hexameric insulin-phenol complex.
  Biophys J, 95, 4193-4204.  
18409193 M.R.Jensen, S.M.Kristensen, C.Keeler, H.E.Christensen, M.E.Hodsdon, and J.J.Led (2008).
Weak self-association of human growth hormone investigated by nitrogen-15 NMR relaxation.
  Proteins, 73, 161-172.  
18332129 Q.X.Hua, S.H.Nakagawa, W.Jia, K.Huang, N.B.Phillips, S.Q.Hu, and M.A.Weiss (2008).
Design of an active ultrastable single-chain insulin analog: synthesis, structure, and therapeutic implications.
  J Biol Chem, 283, 14703-14716.
PDB codes: 2jzq 3bxq
18260111 W.Bocian, J.Sitkowski, A.Tarnowska, E.Bednarek, R.Kawecki, W.Koźmiński, and L.Kozerski (2008).
Direct insight into insulin aggregation by 2D NMR complemented by PFGSE NMR.
  Proteins, 71, 1057-1065.  
15574704 R.Jansen, W.Dzwolak, and R.Winter (2005).
Amyloidogenic self-assembly of insulin aggregates probed by high resolution atomic force microscopy.
  Biophys J, 88, 1344-1353.  
14736893 A.Ahmad, I.S.Millett, S.Doniach, V.N.Uversky, and A.L.Fink (2004).
Stimulation of insulin fibrillation by urea-induced intermediates.
  J Biol Chem, 279, 14999-15013.  
15551269 P.De Meyts (2004).
Insulin and its receptor: structure, function and evolution.
  Bioessays, 26, 1351-1362.  
14988398 Q.X.Hua, and M.A.Weiss (2004).
Mechanism of insulin fibrillation: the structure of insulin under amyloidogenic conditions resembles a protein-folding intermediate.
  J Biol Chem, 279, 21449-21460.
PDB code: 1sf1
12930990 H.B.Olsen, M.R.Leuenberger-Fisher, W.Kadima, D.Borchardt, N.C.Kaarsholm, and M.F.Dunn (2003).
Structural signatures of the complex formed between 3-nitro-4-hydroxybenzoate and the Zn(II)-substituted R(6) insulin hexamer.
  Protein Sci, 12, 1902-1913.  
10547529 Y.K.Cheng, and P.J.Rossky (1999).
The effect of vicinal polar and charged groups on hydrophobic hydration.
  Biopolymers, 50, 742-750.  
9593190 J.Gomar, P.Sodano, D.Sy, D.H.Shin, J.Y.Lee, S.W.Suh, D.Marion, F.Vovelle, and M.Ptak (1998).
Comparison of solution and crystal structures of maize nonspecific lipid transfer protein: a model for a potential in vivo lipid carrier protein.
  Proteins, 31, 160-171.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.