PDBsum entry 1qiy

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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
_CL ×2
Waters ×91
* Residue conservation analysis
PDB id:
Name: Hormone
Title: Human insulin hexamers with chain b his mutated to tyr complexed with phenol
Structure: Insulin a chain. Chain: a, c, e, g, i, k. Synonym: b5tyr_r6_phn. Engineered: yes. Insulin b chain. Chain: b, d, f, h, j, l. Synonym: b5tyr_r6_phn. 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)
2.30Å     R-factor:   0.186    
Authors: L.Tang,J.L.Whittingham,C.S.Verma,L.S.D.Caves,G.G.Dodson
Key ref:
L.Tang et al. (1999). Structural consequences of the B5 histidine --> tyrosine mutation in human insulin characterized by X-ray crystallography and conformational analysis. Biochemistry, 38, 12041-12051. PubMed id: 10508408 DOI: 10.1021/bi990700k
18-Jun-99     Release date:   22-Jun-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: 10.1021/bi990700k Biochemistry 38:12041-12051 (1999)
PubMed id: 10508408  
Structural consequences of the B5 histidine --> tyrosine mutation in human insulin characterized by X-ray crystallography and conformational analysis.
L.Tang, J.L.Whittingham, C.S.Verma, L.S.Caves, G.G.Dodson.
The addition of phenols to hexameric insulin solutions produces a particularly stable hexamer, resulting from a rearrangement in which residues B1-B8 change from an extended conformation (T-state) to form an alpha-helix (R-state). The R-state is, in part, stabilized by nonpolar interactions between the phenolic molecule and residue B5 His at the dimer-dimer interface. The B5 His --> Tyr mutant human insulin was constructed to see if the tyrosine side chain would mimic the effect of phenol binding in the hexamer and induce the R-state. In partial support of this hypothesis, the molecule crystallized as a half-helical hexamer (T(3)R(3)) in conditions that conventionally promote the fully nonhelical (T6) form. As expected, in the presence of phenol or resorcinol, the B5 Tyr hexamers adopt the fully helical (R6) conformation. Molecular modeling calculations were performed to investigate the conformational preference of the T-state B5 Tyr side chain in the T(3)R(3) form, this side chain being associated with structural perturbations of the A7-A10 loop in an adjacent hexamer. For an isolated dimer, several different orientations of the side chain were found, which were close in energy and readily interconvertible. In the crystal environment only one of these conformations remains low in energy; this conformation corresponds to that observed in the crystal structure. This suggests that packing constraints around residue B5 Tyr result in the observed structural rearrangements. Thus, rather than promoting the R-state in a manner analogous to phenol, the mutation appears to destabilize the T-state. These studies highlight the role of B5 His in determining hexamer conformation and in mediating crystal packing interactions, properties that are likely be important in vivo.

Literature references that cite this PDB file's key reference

  PubMed id Reference
11402063 B.Zhang, A.Chang, T.B.Kjeldsen, and P.Arvan (2001).
Intracellular retention of newly synthesized insulin in yeast is caused by endoproteolytic processing in the Golgi complex.
  J Cell Biol, 153, 1187-1198.  
11251810 K.Karata, C.S.Verma, A.J.Wilkinson, and T.Ogura (2001).
Probing the mechanism of ATP hydrolysis and substrate translocation in the AAA protease FtsH by modelling and mutagenesis.
  Mol Microbiol, 39, 890-903.  
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