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PDBsum entry 2ws1

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protein ligands Protein-protein interface(s) links
Hormone PDB id
2ws1
Jmol
Contents
Protein chains
21 a.a.
27 a.a. *
Ligands
ACT
Waters ×41
* Residue conservation analysis
PDB id:
2ws1
Name: Hormone
Title: Semi-synthetic analogue of human insulin nmetyrb26-insulin in monomer form
Structure: Insulin a chain. Chain: a. Insulin b chain. Chain: b. Other_details: methylation of b26 peptide nitrogen atom in b chain of human insulin
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Organism_taxid: 9606
Resolution:
1.60Å     R-factor:   0.187     R-free:   0.247
Authors: A.M.Brzozowski,J.Jiracek,L.Zakova,E.Antolikova,C.J.Watson, J.P.Turkenburg,G.G.Dodson
Key ref: J.Jirácek et al. (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. PubMed id: 20133841
Date:
03-Sep-09     Release date:   09-Feb-10    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01308  (INS_HUMAN) -  Insulin
Seq:
Struc:
110 a.a.
21 a.a.
Protein chain
Pfam   ArchSchema ?
P01308  (INS_HUMAN) -  Insulin
Seq:
Struc:
110 a.a.
27 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  

 

 
Proc Natl Acad Sci U S A 107:1966-1970 (2010)
PubMed id: 20133841  
 
 
Implications for the active form of human insulin based on the structural convergence of highly active hormone analogues.
J.Jirácek, L.Záková, E.Antolíková, C.J.Watson, J.P.Turkenburg, G.G.Dodson, A.M.Brzozowski.
 
  ABSTRACT  
 
Insulin is a key protein hormone that regulates blood glucose levels and, thus, has widespread impact on lipid and protein metabolism. Insulin action is manifested through binding of its monomeric form to the Insulin Receptor (IR). At present, however, our knowledge about the structural behavior of insulin is based upon inactive, multimeric, and storage-like states. The active monomeric structure, when in complex with the receptor, must be different as the residues crucial for the interactions are buried within the multimeric forms. Although the exact nature of the insulin's induced-fit is unknown, there is strong evidence that the C-terminal part of the B-chain is a dynamic element in insulin activation and receptor binding. Here, we present the design and analysis of highly active (200-500%) insulin analogues that are truncated at residue 26 of the B-chain (B(26)). They show a structural convergence in the form of a new beta-turn at B(24)-B(26). We propose that the key element in insulin's transition, from an inactive to an active state, may be the formation of the beta-turn at B(24)-B(26) associated with a trans to cis isomerisation at the B(25)-B(26) peptide bond. Here, this turn is achieved with N-methylated L-amino acids adjacent to the trans to cis switch at the B(25)-B(26) peptide bond or by the insertion of certain D-amino acids at B(26). The resultant conformational changes unmask previously buried amino acids that are implicated in IR binding and provide structural details for new approaches in rational design of ligands effective in combating diabetes.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
23302862 J.G.Menting, J.Whittaker, M.B.Margetts, L.J.Whittaker, G.K.Kong, B.J.Smith, C.J.Watson, L.Záková, E.Kletvíková, J.Jiráček, S.J.Chan, D.F.Steiner, G.G.Dodson, A.M.Brzozowski, M.A.Weiss, C.W.Ward, and M.C.Lawrence (2013).
How insulin engages its primary binding site on the insulin receptor.
  Nature, 493, 241-245.
PDB codes: 3w11 3w12 3w13 3w14
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.