PDBsum entry 1hls

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protein Protein-protein interface(s) links
Hormone PDB id
Protein chains
21 a.a.
30 a.a. *
* Residue conservation analysis
PDB id:
Name: Hormone
Title: Nmr structure of the human insulin-his(b16)
Structure: Insulin. Chain: a. Engineered: yes. Mutation: yes. Insulin. Chain: b. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: pancreas. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932. Expression_system_taxid: 4932
NMR struc: 20 models
Authors: S.Ludvigsen,N.C.Kaarsholm
Key ref:
S.Ludvigsen et al. (1994). High-resolution structure of an engineered biologically potent insulin monomer, B16 Tyr-->His, as determined by nuclear magnetic resonance spectroscopy. Biochemistry, 33, 7998-8006. PubMed id: 8025104 DOI: 10.1021/bi00192a003
28-Jun-95     Release date:   15-Sep-95    
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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.
30 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 1 residue position (black cross)

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


DOI no: 10.1021/bi00192a003 Biochemistry 33:7998-8006 (1994)
PubMed id: 8025104  
High-resolution structure of an engineered biologically potent insulin monomer, B16 Tyr-->His, as determined by nuclear magnetic resonance spectroscopy.
S.Ludvigsen, M.Roy, H.Thøgersen, N.C.Kaarsholm.
Site-directed mutagenesis is used in conjunction with 1H nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy in order to find an insulin species amenable for structure determination in aqueous solution by NMR spectroscopy. A successful candidate in this respect, i.e., B16 Tyr-->His mutant insulin, is identified and selected for detailed characterization by two-dimensional 1H NMR. This mutant species retains 43% biological potency and native folding stability, but in contrast to human insulin it remains monomeric at millimolar concentration in aqueous solution at pH 2.4. The resulting homogeneous sample allows high-quality 2D NMR spectra to be recorded. The NMR studies result in an almost complete assignment of the 1H resonance signals as well as identification of NOE cross peaks. NOE-derived distance restraints in conjunction with torsion restraints based on measured coupling constants, 3JHNH alpha, are used for structure calculations using the hybrid method of distance geometry and simulated annealing. The calculated structures show that the major part of the insulin monomer is structurally well-defined with an average rms deviation between the 20 calculated structures and the mean coordinates of 0.89 A for all backbone atoms, 0.46 A for backbone atoms (A2-A19 and B4-B28), and 1.30 A for all heavy atoms. The structure of the A-chain is composed of two helices from A2 to A7 and from A12 to A19 connected by a short extended strand. The B-chain consists of a loop, B1-B8, an alpha-helix, B9-B19, a beta-turn, B20-B23, and an extended strand from B24 to B30.(ABSTRACT TRUNCATED AT 250 WORDS)

Literature references that cite this PDB file's key reference

  PubMed id Reference
20133841 J.Jirácek, L.Záková, E.Antolíková, C.J.Watson, J.P.Turkenburg, G.G.Dodson, and A.M.Brzozowski (2010).
Implications for the active form of human insulin based on the structural convergence of highly active hormone analogues.
  Proc Natl Acad Sci U S A, 107, 1966-1970.
PDB codes: 2wru 2wrv 2wrw 2wrx 2ws0 2ws1 2ws4 2ws6 2ws7
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.  
19670911 J.J.Hull, K.S.Copley, K.M.Schegg, D.R.Quilici, D.A.Schooley, and W.H.Welch (2009).
De novo molecular modeling and biophysical characterization of Manduca sexta eclosion hormone.
  Biochemistry, 48, 9047-9060.  
18040865 W.Bocian, J.Sitkowski, E.Bednarek, A.Tarnowska, R.Kawecki, and L.Kozerski (2008).
Structure of human insulin monomer in water/acetonitrile solution.
  J Biomol NMR, 40, 55-64.
PDB code: 2jv1
18491415 W.Bocian, P.Borowicz, J.Mikołajczyk, J.Sitkowski, A.Tarnowska, E.Bednarek, T.Głabski, B.Tejchman-Małecka, M.Bogiel, and L.Kozerski (2008).
NMR structure of biosynthetic engineered human insulin monomer B31(Lys)-B32(Arg) in water/acetonitrile solution. Comparison with the solution structure of native human insulin monomer.
  Biopolymers, 89, 820-830.
PDB code: 2rn5
16627943 J.L.Whittingham, Z.Youshang, L.Záková, E.J.Dodson, J.P.Turkenburg, J.Brange, and G.G.Dodson (2006).
I222 crystal form of despentapeptide (B26-B30) insulin provides new insights into the properties of monomeric insulin.
  Acta Crystallogr D Biol Crystallogr, 62, 505-511.
PDB code: 2ceu
15880782 T.Inaba, S.Tahara, N.Nisikawa, H.Kashiwagi, and F.Sato (2005).
All-electron density functional calculation on insulin with quasi-canonical localized orbitals.
  J Comput Chem, 26, 987-993.  
16080143 V.Zoete, M.Meuwly, and M.Karplus (2005).
Study of the insulin dimerization: binding free energy calculations and per-residue free energy decomposition.
  Proteins, 61, 79-93.  
11923277 T.Kjeldsen, S.Ludvigsen, I.Diers, P.Balschmidt, A.R.Sorensen, and N.C.Kaarsholm (2002).
Engineering-enhanced protein secretory expression in yeast with application to insulin.
  J Biol Chem, 277, 18245-18248.  
11352739 L.Nielsen, R.Khurana, A.Coats, S.Frokjaer, J.Brange, S.Vyas, V.N.Uversky, and A.L.Fink (2001).
Effect of environmental factors on the kinetics of insulin fibril formation: elucidation of the molecular mechanism.
  Biochemistry, 40, 6036-6046.  
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.  
11123908 S.H.Nakagawa, H.S.Tager, and D.F.Steiner (2000).
Mutational analysis of invariant valine B12 in insulin: implications for receptor binding.
  Biochemistry, 39, 15826-15835.  
  10091652 G.Kurapkat, M.Siedentop, H.G.Gattner, M.Hagelstein, D.Brandenburg, J.Grötzinger, and A.Wollmer (1999).
The solution structure of a superpotent B-chain-shortened single-replacement insulin analogue.
  Protein Sci, 8, 499-508.
PDB code: 1bzv
9566117 C.McInnes, and B.D.Sykes (1997).
Growth factor receptors: structure, mechanism, and drug discovery.
  Biopolymers, 43, 339-366.  
9335531 C.R.Bloom, R.Heymann, N.C.Kaarsholm, and M.F.Dunn (1997).
Binding of 2,6- and 2,7-dihydroxynaphthalene to wild-type and E-B13Q insulins: dynamic, equilibrium, and molecular modeling investigations.
  Biochemistry, 36, 12746-12758.  
  9070440 G.Kurapkat, E.De Wolf, J.Grötzinger, and A.Wollmer (1997).
Inactive conformation of an insulin despite its wild-type sequence.
  Protein Sci, 6, 580-587.  
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.  
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
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.