PDBsum entry 1nau

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Hormone/growth factor PDB id
Protein chain
28 a.a.
PDB id:
Name: Hormone/growth factor
Title: Nmr solution structure of the glucagon antagonist [deshis1, desphe6, glu9]glucagon amide in the presence of perdeuterated dodecylphosphocholine micelles
Structure: Glucagon. Chain: a. Synonym: glicentin-related polypeptide (grpp). Engineered: yes. Mutation: yes
Source: Synthetic: yes. Other_details: this sequence was chemically synthesized. It was obtained by modifying the sequence of glucagon, which occurs naturally in homo sapiens (human).
NMR struc: 16 models
Authors: J.Ying,J.-M.Ahn,N.E.Jacobsen,M.F.Brown,V.J.Hruby
Key ref:
J.Ying et al. (2003). NMR solution structure of the glucagon antagonist [desHis1, desPhe6, Glu9]glucagon amide in the presence of perdeuterated dodecylphosphocholine micelles. Biochemistry, 42, 2825-2835. PubMed id: 12627948 DOI: 10.1021/bi026629r
28-Nov-02     Release date:   18-Mar-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P01275  (GLUC_HUMAN) -  Glucagon
180 a.a.
28 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 2 residue positions (black crosses)


DOI no: 10.1021/bi026629r Biochemistry 42:2825-2835 (2003)
PubMed id: 12627948  
NMR solution structure of the glucagon antagonist [desHis1, desPhe6, Glu9]glucagon amide in the presence of perdeuterated dodecylphosphocholine micelles.
J.Ying, J.M.Ahn, N.E.Jacobsen, M.F.Brown, V.J.Hruby.
Glucagon, a 29-residue peptide hormone, plays an important role in glucose homeostasis and in diabetes mellitus. Several glucagon antagonists and agonists have been developed, but limited structural information is available to clarify the basis of their biological activity. The solution structure of the potent glucagon antagonist, [desHis1, desPhe6, Glu9]glucagon amide, was determined by homonuclear 2D NMR spectroscopy at pH 6.0 and 37 degrees C in perdeuterated dodecylphosphocholine micelles. The overall backbone root-mean-square deviation (rmsd) for the structured portion (residues 7-29, glucagon numbering) of the micelle-bound 27-residue peptide is 1.36 A for the 15 lowest-energy structures, after restrained molecular dynamics simulation. The structure consists of four regions (segment backbone rmsd in A): an unstructured N-terminal segment between residues 2 and 5 (1.68), an irregular helix between residues 7 and 14 (0.79), a hinge region between residues 15 and 18 (0.54), and a well-defined alpha-helix between residues 19 and 29 (0.33). The two helices form an L-shaped structure with an angle of about 90 degrees between the helix axes. There is an extended hydrophobic cluster, which runs along the inner surface of the L-structure and incorporates the side chains of the hydrophobic residues of each of the amphipathic helices. The outer surface contains the hydrophilic side chains, with two salt bridges (D15-R18 and R17-D21) implied from close approach of the charged groups. This result is the first clear indication of an overall tertiary fold for a glucagon analogue in the micelle-bound state. The relationship of the two helical structural elements may have important implications for the biological activity of the glucagon antagonist.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20453923 D.N.Langelaan, and J.K.Rainey (2010).
Membrane catalysis of peptide-receptor binding.
  Biochem Cell Biol, 88, 203-210.  
18821747 T.Yamamoto, P.Nair, N.E.Jacobsen, P.Davis, S.W.Ma, E.Navratilova, S.Moye, J.Lai, H.I.Yamamura, T.W.Vanderah, F.Porreca, and V.J.Hruby (2008).
The importance of micelle-bound states for the bioactivities of bifunctional peptide derivatives for delta/mu opioid receptor agonists and neurokinin 1 receptor antagonists.
  J Med Chem, 51, 6334-6347.  
16505481 C.Q.Pan, J.M.Buxton, S.L.Yung, I.Tom, L.Yang, H.Chen, M.MacDougall, A.Bell, T.H.Claus, K.B.Clairmont, and J.P.Whelan (2006).
Design of a long acting peptide functioning as both a glucagon-like peptide-1 receptor agonist and a glucagon receptor antagonist.
  J Biol Chem, 281, 12506-12515.  
17073452 S.Abu-Baker, and G.A.Lorigan (2006).
Phospholamban and its phosphorylated form interact differently with lipid bilayers: a 31P, 2H, and 13C solid-state NMR spectroscopic study.
  Biochemistry, 45, 13312-13322.  
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