PDBsum entry 2vk0

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protein ligands metals Protein-protein interface(s) links
Hormone PDB id
Protein chains
21 a.a.
28 a.a. *
27 a.a. *
_ZN ×4
Waters ×66
* Residue conservation analysis
PDB id:
Name: Hormone
Title: Crystal structure form ultalente insulin microcrystals
Structure: Insulin a chain. Chain: a, c. Fragment: residues 90-110. Engineered: yes. Other_details: ultralente insulin crystals. Insulin b chain. Chain: b, d. Fragment: residues 25-54. Engineered: yes.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932. Expression_system_taxid: 4932
2.20Å     R-factor:   0.242     R-free:   0.282
Authors: A.Wagner,J.Diez,C.Schulze-Briese,G.Schluckebier
Key ref:
A.Wagner et al. (2008). Crystal structure of Ultralente-A microcrystalline insulin suspension. Proteins, 74, 1018-1027. PubMed id: 18767151 DOI: 10.1002/prot.22213
14-Dec-07     Release date:   16-Sep-08    
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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.
28 a.a.
Protein chain
Pfam   ArchSchema ?
P01308  (INS_HUMAN) -  Insulin
110 a.a.
27 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: 10.1002/prot.22213 Proteins 74:1018-1027 (2008)
PubMed id: 18767151  
Crystal structure of Ultralente-A microcrystalline insulin suspension.
A.Wagner, J.Diez, C.Schulze-Briese, G.Schluckebier.
Ultralente insulin has been one of the commercially most important insulin preparations in diabetes treatment over the last 50 years. It is a suspension of insulin microcrystals which dissolve slowly following subcutaneous injection. Because of the small crystal size of about 25 x 25 x 5 mum(3) the atomic structure has been elusive until now. Here we present the crystal structures from Ultralente and their precursor microcrystals from the industrial manufacturing process. During this process insulin undergoes a conformational change within the microcrystals. Both structures show canonical folding of the insulin molecules but exhibit a number of new features when compared with other insulin structures. Surprisingly, we found that the Ultralente crystals bind the conservation agent methylparaben, which slows down dissolution of the crystals and thus contributes to the long duration of action. Proteins 2009. (c) 2008 Wiley-Liss, Inc.
  Selected figure(s)  
Figure 5.
Figure 5. Zinc coordination in the precursor crystals. (a) Location of zinc (grey spheres) in the insulin hexamer. Off-axis zinc are coordinated by His B10 (sidechains drawn in purple) and His B5 (pink) from different monomers, whereas the on-axis Zinc is coordinated by His B10 (sidechains in yellow) only. The protein is drawn in a ribbon representation, with the three different dimers coloured in yellow/green, orange/red and cyan/blue, respectively. (b) Zinc coordination in the off-axis binding site. Zinc is depicted as a grey sphere, chloride as green spheres. The electron density has been calculated with zinc and chloride atoms omitted in the structure factor calculation. Shown is a 2F[o] - F[c] map at two sigma (green) and an F[o] - F[c] map (red) at five sigma level. (c) Superposition of the m-cresol binding site of R[6] insulin[29] (magenta) with the off-axis zinc binding site in the precursor crystals, drawn in grey. Cresol is shown in magenta, zinc and chloride ions are drawn as grey and green spheres, respectively.
Figure 7.
Figure 7. Binding of methylparaben (MPO) to the Ultralente crystals. (a) Location of the methylparaben binding sites on the dimer-dimer interfaces of the hexamer. The A-chains of the insulin hexamer are drawn in yellow, the B-chains in blue. MPO is orange. The darker shades of yellow and blue indicate the trimer which underwent the R to T transition in the crystals. (b) Close-up of the methylparaben binding site. Methylparaben is in two orientations, shown in yellow and pink, respectively. The interacting amino acids Leu A13, Tyr A14 and Glu A17 are shown in stick representation and color coded according to the molecule they belong to (blue and cyan).
  The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2008, 74, 1018-1027) copyright 2008.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19929835 C.L.Verlinde, E.Fan, S.Shibata, Z.Zhang, Z.Sun, W.Deng, J.Ross, J.Kim, L.Xiao, T.L.Arakaki, J.Bosch, J.M.Caruthers, E.T.Larson, I.Letrong, A.Napuli, A.Kelly, N.Mueller, F.Zucker, W.C.Van Voorhis, E.A.Merritt, and W.G.Hol (2009).
Fragment-based cocktail crystallography by the medical structural genomics of pathogenic protozoa consortium.
  Curr Top Med Chem, 9, 1678-1687.  
19855826 W.C.Van Voorhis, W.G.Hol, P.J.Myler, and L.J.Stewart (2009).
The role of medical structural genomics in discovering new drugs for infectious diseases.
  PLoS Comput Biol, 5, e1000530.
PDB codes: 3eiy 3ej0
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