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PDBsum entry 3zqr

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protein ligands metals Protein-protein interface(s) links
Hormone PDB id
3zqr
Jmol
Contents
Protein chains
(+ 0 more) 21 a.a.
29 a.a.
28 a.a.
27 a.a.
28 a.a.
Ligands
IPH ×6
Metals
_CL ×2
_ZN ×2
Waters ×106
PDB id:
3zqr
Name: Hormone
Title: Nmepheb25 insulin analogue crystal structure
Structure: Insulin a chain. Chain: a, c, e, g, i, k. Insulin b chain. Chain: b, d, f, h, j, l. Synonym: nmeb25phe-insulin. Other_details: the n-peptide atom of phe 25 is methylated
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Organism_taxid: 9606
Resolution:
1.90Å     R-factor:   0.226     R-free:   0.281
Authors: E.Antolikova,L.Zakova,J.P.Turkenburg,C.J.Watson,I.Hanclova,M A.Cooper,T.Kraus,A.M.Brzozowski,J.A.Jiracek
Key ref: E.Antolíková et al. (2011). Non-equivalent role of inter- and intramolecular hydrogen bonds in the insulin dimer interface. J Biol Chem, 286, 36968-36977. PubMed id: 21880708 DOI: 10.1074/jbc.M111.265249
Date:
10-Jun-11     Release date:   24-Aug-11    
PROCHECK
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 Headers
 References

Protein chains
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.
29 a.a.*
Protein chains
Pfam   ArchSchema ?
P01308  (INS_HUMAN) -  Insulin
Seq:
Struc:
110 a.a.
28 a.a.*
Protein chain
Pfam   ArchSchema ?
P01308  (INS_HUMAN) -  Insulin
Seq:
Struc:
110 a.a.
27 a.a.*
Protein chains
Pfam   ArchSchema ?
P01308  (INS_HUMAN) -  Insulin
Seq:
Struc:
110 a.a.
28 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biochemical function     hormone activity     1 term  

 

 
DOI no: 10.1074/jbc.M111.265249 J Biol Chem 286:36968-36977 (2011)
PubMed id: 21880708  
 
 
Non-equivalent role of inter- and intramolecular hydrogen bonds in the insulin dimer interface.
E.Antolíková, L.Žáková, J.P.Turkenburg, C.J.Watson, I.Hančlová, M.Šanda, A.Cooper, T.Kraus, A.M.Brzozowski, J.Jiráček.
 
  ABSTRACT  
 
Apart from its role in insulin receptor (IR) activation, the C terminus of the B-chain of insulin is also responsible for the formation of insulin dimers. The dimerization of insulin plays an important role in the endogenous delivery of the hormone and in the administration of insulin to patients. Here, we investigated insulin analogues with selective N-methylations of peptide bond amides at positions B24, B25, or B26 to delineate their structural and functional contribution to the dimer interface. All N-methylated analogues showed impaired binding affinities to IR, which suggests a direct IR-interacting role for the respective amide hydrogens. The dimerization capabilities of analogues were investigated by isothermal microcalorimetry. Selective N-methylations of B24, B25, or B26 amides resulted in reduced dimerization abilities compared with native insulin (K(d) = 8.8 μM). Interestingly, although the N-methylation in [NMeTyrB26]-insulin or [NMePheB24]-insulin resulted in K(d) values of 142 and 587 μM, respectively, the [NMePheB25]-insulin did not form dimers even at high concentrations. This effect may be attributed to the loss of intramolecular hydrogen bonding between NHB25 and COA19, which connects the B-chain β-strand to the core of the molecule. The release of the B-chain β-strand from this hydrogen bond lock may result in its higher mobility, thereby shifting solution equilibrium toward the monomeric state of the hormone. The study was complemented by analyses of two novel analogue crystal structures. All examined analogues crystallized only in the most stable R(6) form of insulin oligomers (even if the dimer interface was totally disrupted), confirming the role of R(6)-specific intra/intermolecular interactions for hexamer stability.