PDBsum entry 2wrx

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protein metals Protein-protein interface(s) links
Hormone PDB id
Protein chains
21 a.a.
27 a.a. *
Waters ×101
* Residue conservation analysis
PDB id:
Name: Hormone
Title: Semi-synthetic analogue of human insulin nmealab26-insulin at ph 3.0
Structure: Insulin a chain. Chain: a, c. Insulin b chain. Chain: b, d. Mutation: yes. Other_details: methylation of b26 and d26 peptide nitrogen atom in b and d chain of human insulin
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Organism_taxid: 9606
1.50Å     R-factor:   0.183     R-free:   0.250
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
02-Sep-09     Release date:   09-Feb-10    
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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.
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.
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
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