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PDBsum entry 2kqp

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protein links
Hormone PDB id
2kqp
Jmol
Contents
Protein chain
86 a.a. *
* Residue conservation analysis
PDB id:
2kqp
Name: Hormone
Title: Nmr structure of proinsulin
Structure: Insulin. Chain: a. Synonym: insulin b chain, insulin a chain. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ins. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 20 models
Authors: Y.Yang,Q.X.Hua,R.B.Mackin,M.A.Weiss
Key ref: Y.Yang et al. (2010). Solution structure of proinsulin: connecting domain flexibility and prohormone processing. J Biol Chem, 285, 7847-7851. PubMed id: 20106974
Date:
12-Nov-09     Release date:   26-Jan-10    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01308  (INS_HUMAN) -  Insulin
Seq:
Struc:
110 a.a.
86 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   6 terms 
  Biological process     small molecule metabolic process   62 terms 
  Biochemical function     protein binding     6 terms  

 

 
J Biol Chem 285:7847-7851 (2010)
PubMed id: 20106974  
 
 
Solution structure of proinsulin: connecting domain flexibility and prohormone processing.
Y.Yang, Q.X.Hua, J.Liu, E.H.Shimizu, M.H.Choquette, R.B.Mackin, M.A.Weiss.
 
  ABSTRACT  
 
The folding of proinsulin, the single-chain precursor of insulin, ensures native disulfide pairing in pancreatic beta-cells. Mutations that impair folding cause neonatal diabetes mellitus. Although the classical structure of insulin is well established, proinsulin is refractory to crystallization. Here, we employ heteronuclear NMR spectroscopy to characterize a monomeric analogue. Proinsulin contains a native-like insulin moiety (A- and B-domains); the tethered connecting (C) domain (as probed by {(1)H}-(15)N nuclear Overhauser enhancements) is progressively less ordered. Although the BC junction is flexible, residues near the CA junction exhibit alpha-helical-like features. Relative to canonical alpha-helices, however, segmental (13)C(alpha/beta) chemical shifts are attenuated, suggesting that this junction and contiguous A-chain residues are molten. We propose that flexibility at each C-domain junction facilitates prohormone processing. Studies of protease SPC3 (PC1/3) suggest that C-domain sequences contribute to cleavage site selection. The structure of proinsulin provides a foundation for studies of insulin biosynthesis and its impairment in monogenic forms of diabetes mellitus.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21388412 N.G.Seidah (2011).
What lies ahead for the proprotein convertases?
  Ann N Y Acad Sci, 1220, 149-161.  
20877850 S.Luisier, M.Avital-Shmilovici, M.A.Weiss, and S.B.Kent (2010).
Total chemical synthesis of human proinsulin.
  Chem Commun (Camb), 46, 8177-8179.  
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