PDBsum entry 1his

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protein Protein-protein interface(s) links
Hormone PDB id
Protein chains
21 a.a.
25 a.a.
PDB id:
Name: Hormone
Title: Structure and dynamics of des-pentapeptide-insulin in solution: the molten-globule hypothesis.
Structure: Insulin. Chain: a. Engineered: yes. Insulin. Chain: b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: pancreas
NMR struc: 15 models
Authors: Q.X.Hua,M.Kochoyan,M.A.Weiss
Key ref: Q.X.Hua et al. (1992). Structure and dynamics of des-pentapeptide-insulin in solution: the molten-globule hypothesis. Proc Natl Acad Sci U S A, 89, 2379-2383. PubMed id: 1549601 DOI: 10.1073/pnas.89.6.2379
28-Feb-92     Release date:   31-Jan-94    
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Protein chain
Pfam   ArchSchema ?
P01308  (INS_HUMAN) -  Insulin
110 a.a.
21 a.a.
Protein chain
Pfam   ArchSchema ?
P01308  (INS_HUMAN) -  Insulin
110 a.a.
25 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.89.6.2379 Proc Natl Acad Sci U S A 89:2379-2383 (1992)
PubMed id: 1549601  
Structure and dynamics of des-pentapeptide-insulin in solution: the molten-globule hypothesis.
Q.X.Hua, M.Kochoyan, M.A.Weiss.
Structures of insulin in different crystal forms exhibit significant local and nonlocal differences, including correlated displacement of elements of secondary structure. Here we describe the solution structure and dynamics of a monomeric insulin analogue, des-pentapeptide-(B26-B30)-insulin (DPI), as determined by two-dimensional NMR spectroscopy and distance geometry/restrained molecular dynamics (DG/RMD). Although the solution structure of DPI exhibits a general similarity to its crystal structure, individual DG/RMD structures in the NMR ensemble differ by rigid-body displacements of alpha-helices that span the range of different crystal forms. These results suggest that DPI exists as a partially folded state formed by coalescence of distinct alpha-helix-associated microdomains. The physical reality of this model is investigated by comparison of the observed two-dimensional nuclear Overhauser enhancement (NOE) spectroscopy (NOESY) spectrum with that predicted from crystal and DG/RMD structures. The observed NOESY spectrum contains fewer tertiary contacts than predicted by any single simulation, but it matches their shared features; such "ensemble correspondence" is likely to reflect the effect of protein dynamics on observed NOE intensities. We propose (i) that the folded state of DPI is analogous to that of a compact protein-folding intermediate rather than a conventional native state and (ii) that the molten state is the biologically active species. This proposal (the molten-globule hypothesis) leads to testable thermodynamic predictions and has general implications for protein design.

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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
18492668 Z.L.Wan, K.Huang, S.Q.Hu, J.Whittaker, and M.A.Weiss (2008).
The structure of a mutant insulin uncouples receptor binding from protein allostery. An electrostatic block to the TR transition.
  J Biol Chem, 283, 21198-21210.  
15895384 B.Franke, T.S.Galloway, and T.J.Wilkin (2005).
Developments in the prediction of type 1 diabetes mellitus, with special reference to insulin autoantibodies.
  Diabetes Metab Res Rev, 21, 395-415.  
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
11742127 B.Xu, Q.X.Hua, S.H.Nakagawa, W.Jia, Y.C.Chu, P.G.Katsoyannis, and M.A.Weiss (2002).
A cavity-forming mutation in insulin induces segmental unfolding of a surrounding alpha-helix.
  Protein Sci, 11, 104-116.
PDB code: 1k3m
12081626 F.Y.Dupradeau, T.Richard, G.Le Flem, H.Oulyadi, Y.Prigent, and J.P.Monti (2002).
A new B-chain mutant of insulin: comparison with the insulin crystal structure and role of sulfonate groups in the B-chain structure.
  J Pept Res, 60, 56-64.
PDB code: 1ho0
9671699 M.C.Lo, S.Ha, I.Pelczer, S.Pal, and S.Walker (1998).
The solution structure of the DNA-binding domain of Skn-1.
  Proc Natl Acad Sci U S A, 95, 8455-8460.  
9131992 I.Pittman, S.H.Nakagawa, H.S.Tager, and D.F.Steiner (1997).
Maintenance of the B-chain beta-turn in [GlyB24] insulin mutants: a steady-state fluorescence anisotropy study.
  Biochemistry, 36, 3430-3437.  
9236009 J.Zurdo, J.M.Sanz, C.González, M.Rico, and J.P.Ballesta (1997).
The exchangeable yeast ribosomal acidic protein YP2beta shows characteristics of a partly folded state under physiological conditions.
  Biochemistry, 36, 9625-9635.  
9235985 X.Chang, A.M.Jorgensen, P.Bardrum, and J.J.Led (1997).
Solution structures of the R6 human insulin hexamer,.
  Biochemistry, 36, 9409-9422.
PDB codes: 1ai0 1aiy
  7613459 K.A.Dill, S.Bromberg, K.Yue, K.M.Fiebig, D.P.Yee, P.D.Thomas, and H.S.Chan (1995).
Principles of protein folding--a perspective from simple exact models.
  Protein Sci, 4, 561-602.  
  7527339 H.Terasawa, D.Kohda, H.Hatanaka, K.Nagata, N.Higashihashi, H.Fujiwara, K.Sakano, and F.Inagaki (1994).
Solution structure of human insulin-like growth factor II; recognition sites for receptors and binding proteins.
  EMBO J, 13, 5590-5597.  
8332604 D.T.Haynie, and E.Freire (1993).
Structural energetics of the molten globule state.
  Proteins, 16, 115-140.  
  8380086 L.D.Chong, and J.K.Rose (1993).
Membrane association of functional vesicular stomatitis virus matrix protein in vivo.
  J Virol, 67, 407-414.  
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.