PDBsum entry 1b9e

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Hormone/growth factor PDB id
Protein chains
21 a.a.
30 a.a. *
Waters ×45
* Residue conservation analysis
PDB id:
Name: Hormone/growth factor
Title: Human insulin mutant serb9glu
Structure: Protein (insulin). Chain: a, c. Engineered: yes. Protein (insulin). Chain: b, d. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932. Expression_system_taxid: 4932
Biol. unit: Tetramer (from PQS)
2.50Å     R-factor:   0.165     R-free:   0.264
Authors: D.C.Wang,Z.H.Zeng,Z.P.Yao,H.M.Li
Key ref:
Z.P.Yao et al. (1999). Structure of an insulin dimer in an orthorhombic crystal: the structure analysis of a human insulin mutant (B9 Ser-->Glu). Acta Crystallogr D Biol Crystallogr, 55, 1524-1532. PubMed id: 10489447 DOI: 10.1107/S0907444999008562
12-Nov-98     Release date:   17-Nov-99    
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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
* 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: 10.1107/S0907444999008562 Acta Crystallogr D Biol Crystallogr 55:1524-1532 (1999)
PubMed id: 10489447  
Structure of an insulin dimer in an orthorhombic crystal: the structure analysis of a human insulin mutant (B9 Ser-->Glu).
Z.P.Yao, Z.H.Zeng, H.M.Li, Y.Zhang, Y.M.Feng, D.C.Wang.
The structure of human insulin mutant B9 (Ser-->Glu) was determined by an X-ray crystallographic method at 2.5 A resolution with an R factor of 0.165 under non-crystallographic restraints. The crystals were grown at low pH (<3.8) and belong to the orthorhombic P2(1)2(1)2(1) space group with unit-cell dimensions a = 44.54, b = 46.40, c = 51.85 A and one dimer per asymmetric unit without further aggregation. The structure in this crystal form can be regarded as a model for a discrete insulin dimer and displays the following features compared with the structure of 2Zn insulin. (i) The overall dimer is expanded and more symmetric. The two A chains are about 2 A more distant from each other, while the two B chains are about 0.8 A further apart. Both monomers are more similar to molecule 1 than molecule 2 of the 2Zn insulin dimer. (ii) The dimer structure is stabilized by protonation and neutralization of the carboxyl groups at lower pH and, in addition, by formation of a hydrogen-bond network among the side chains of residues GluB9, HisB13 and HisB10 on the dimer-forming surface of both monomers, resulting from a structural rearrangement. (iii) The B-chain amino-terminal segment is in an open state (O state), i.e. a state different from the well known R and T states found in the insulin hexamer. In the O state, the B-chain N-terminal segment is in an extended conformation and is detached from the rest of the molecule. This conformational state has also been observed in the monomeric crystal structure of despentapeptide (B26-B30) and desheptapeptide (B24-B30) insulin, as well as in the solution structure of an engineered insulin monomer. It suggests that the O state may be the characteristic conformation of insulin in lower aggregation forms and may be relevant to the formation of insulin fibrils. In addition, based on the crystallization process, the smallest possible building blocks of insulin crystal are also discussed.
  Selected figure(s)  
Figure 7.
Figure 7 Hydrogen-bond network among side chains of B9, B10 and B13 from both monomers at the dimer-forming surface. Distances are in .
Figure 8.
Figure 8 Conformational comparison of B-chain N-terminal residues, showing the O state (a) in the crystal and (b) in solution. (a) Overlapped structures of B9E HI (red), DPI (blue), DHPI (green). (b) The 25 NMR structures (green) of engineered (B1, B10, B16, B27)Glu, des B30-insulin overlapped on B9E HI (red). The coordinates of DPI, DHPI and (B1, B10, B16, B27)Glu, des B30-insulin are taken from the Protein Data Bank, with codes 1pid, 1dei and 1hui, respectively.
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (1999, 55, 1524-1532) copyright 1999.  
  Figures were selected by an automated process.  

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.  
16246845 A.Ahmad, V.N.Uversky, D.Hong, and A.L.Fink (2005).
Early events in the fibrillation of monomeric insulin.
  J Biol Chem, 280, 42669-42675.  
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.  
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.  
12446709 B.Y.Zhang, M.Liu, and P.Arvan (2003).
Behavior in the eukaryotic secretory pathway of insulin-containing fusion proteins and single-chain insulins bearing various B-chain mutations.
  J Biol Chem, 278, 3687-3693.  
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