spacer
spacer

PDBsum entry 1kx6

Go to PDB code: 
protein links
Hormone/growth factor PDB id
1kx6
Jmol
Contents
Protein chain
29 a.a.
PDB id:
1kx6
Name: Hormone/growth factor
Title: Nmr solution structure of glucagon in a lipid-water interphase
Structure: Glucagon. Chain: a. Engineered: yes
Source: Synthetic: yes. Other_details: this protein was chemically synthesized. It is naturally found in bos taurus (bovine).
NMR struc: 20 models
Authors: W.Braun,G.Wider,K.H.Lee,K.Wuthrich
Key ref:
W.Braun et al. (1983). Conformation of glucagon in a lipid-water interphase by 1H nuclear magnetic resonance. J Mol Biol, 169, 921-948. PubMed id: 6631957 DOI: 10.1016/S0022-2836(83)80143-0
Date:
31-Jan-02     Release date:   13-Feb-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01272  (GLUC_BOVIN) -  Glucagon
Seq:
Struc:
180 a.a.
29 a.a.
Key:    PfamA domain  Secondary structure

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

 

 
DOI no: 10.1016/S0022-2836(83)80143-0 J Mol Biol 169:921-948 (1983)
PubMed id: 6631957  
 
 
Conformation of glucagon in a lipid-water interphase by 1H nuclear magnetic resonance.
W.Braun, G.Wider, K.H.Lee, K.Wüthrich.
 
  ABSTRACT  
 
A determination of the spatial structure of the polypeptide hormone glucagon bound to perdeuterated dodecylphosphocholine micelles is described. A map of distance constraints between individually assigned hydrogen atoms of the polypeptide chain was obtained from two-dimensional nuclear Overhauser enhancement spectroscopy. These data were used as the input for a distance geometry algorithm for computing conformations that would be compatible with the experiments. In the region from residues 5 to 29 the mobility of the polypeptide backbone and most of the amino acid side-chains was found to be essentially restricted to the overall rotational tumbling of the micelles. The secondary structure in this region includes three turns of irregular alpha-helix in the segment of residues 17 to 29 near the C terminus, a stretch of extended polypeptide chain from residues 14 to 17, an alpha-helix-like turn formed by the residues 10 to 14 and another extended region from residues 5 to 10. In the N-terminal tetrapeptide H-His-Ser-Gln-Gly- the two terminal residues are highly mobile, indicating that they extend into the aqueous phase, and the mobility of the residues Gln3 and Gly4 appears to be only partially restricted by the binding to the micelle. The absence of long range nuclear Overhauser effects between the peptide segments 5-9 and 11-29, and between 5-16 and 19-29 shows that the polypeptide chain does not fold back on itself and hence that micelle-bound glucagon does not adopt a globular tertiary structure. Previously it was shown that the polypeptide backbone of glucagon is located close to and runs roughly parallel to the micelle surface. Combination of these observations suggests that the overall spatial arrangement of the glucagon polypeptide chain in a lipid-water interphase is largely determined by the topology of the lipid support, in the present case the curvature of the dodecylphosphocholine micelles. The tertiary structure is further characterized by the formation of two hydrophobic patches by the side-chains of Phe6, Tyr10 and Leu14, and the side-chains of Ala19, Phe22, Val23, Trp25 and Leu26, respectively.
 
  Selected figure(s)  
 
Figure 4.
FIG. 4. Computer drawings of the sptial tructure for 4 segments of MB-glucagon. From th final group of computations for each segment all those strctures that have satisfactory stereochemistry (see the text) are shown superimposed on each other. For each segment drawings of the backbone (B) and of the restrained side-chain presentation (SR) are shown. SR includes the complete sde-chains for the residues tat are identified in the drawings and or which NOE constraints were observed for the peripheral protons (Table 2). Fr the ther residues only the backbone toms, including the C= and amide protons and C p are shown. CH 3 and CH 2 group are represented by the spherical pseudo-atoms M and L, respectively, nd the CH groups in the aromatic rings of Phe and Tyr by the spherical pseudo-atom K (see the text). (a) Segment 19-29, 6 structures are superimposed; (b) segment 17-27, 5 structres; (c) segment 10-20, 5 structures; (d) segment 5-15, 8 structures.
Figure 5.
FIG. 5. Computer drawing of the stereochemically best structure (see the text) fr each segment from the group of molecular geometiesshown n Fig. 4. The SR presentation is shown and the same pseudo-at~oms are usd as in Fig. 4. For each segment mono and a tereo drawing is shown. (a)_Segment 19-29; (b) 17-27; (c) 10-20; (d) 5-15.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1983, 169, 921-948) copyright 1983.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19861722 C.R.Underwood, P.Garibay, L.B.Knudsen, S.Hastrup, G.H.Peters, R.Rudolph, and S.Reedtz-Runge (2010).
Crystal structure of glucagon-like peptide-1 in complex with the extracellular domain of the glucagon-like peptide-1 receptor.
  J Biol Chem, 285, 723-730.
PDB code: 3iol
20453923 D.N.Langelaan, and J.K.Rainey (2010).
Membrane catalysis of peptide-receptor binding.
  Biochem Cell Biol, 88, 203-210.  
19446460 C.Parthier, S.Reedtz-Runge, R.Rudolph, and M.T.Stubbs (2009).
Passing the baton in class B GPCRs: peptide hormone activation via helix induction?
  Trends Biochem Sci, 34, 303-310.  
18339765 A.S.Svane, K.Jahn, T.Deva, A.Malmendal, D.E.Otzen, J.Dittmer, and N.C.Nielsen (2008).
Early stages of amyloid fibril formation studied by liquid-state NMR: the peptide hormone glucagon.
  Biophys J, 95, 366-377.  
18555686 J.M.Neumann, A.Couvineau, S.Murail, J.J.Lacapère, N.Jamin, and M.Laburthe (2008).
Class-B GPCR activation: is ligand helix-capping the key?
  Trends Biochem Sci, 33, 314-319.  
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.  
17437246 A.K.Malde, S.S.Srivastava, and E.C.Coutinho (2007).
Understanding interactions of gastric inhibitory polypeptide (GIP) with its G-protein coupled receptor through NMR and molecular modeling.
  J Pept Sci, 13, 287-300.  
17657708 C.R.Grace, L.Cervini, J.Gulyas, J.Rivier, and R.Riek (2007).
Astressin-amide and astressin-acid are structurally different in dimethylsulfoxide.
  Biopolymers, 87, 196-205.
PDB code: 2rmi
17313206 S.Maddipati, and A.Fernández (2007).
Peptide translocators with engineered dehydration-prone hydrogen bonds.
  J Chem Phys, 126, 061102.  
17051221 Y.Shen, A.Joachimiak, M.R.Rosner, and W.J.Tang (2006).
Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism.
  Nature, 443, 870-874.
PDB codes: 2g47 2g48 2g49 2g54 2g56
15641105 M.Adenot, C.S.de Menthière, A.Kervran, and G.Grassy (2005).
Peptide dynamic fingerprints: a tool for investigating the role of conformational flexibility for GLP-1 analogs affinity.
  J Pept Sci, 11, 463-471.  
14645089 I.R.Chandrashekar, and S.M.Cowsik (2003).
Three-dimensional structure of the mammalian tachykinin peptide neurokinin A bound to lipid micelles.
  Biophys J, 85, 4002-4011.
PDB code: 1n6t
12524318 R.C.Grace, I.R.Chandrashekar, and S.M.Cowsik (2003).
Solution structure of the tachykinin peptide eledoisin.
  Biophys J, 84, 655-664.
PDB code: 1mxq
12724331 S.Runge, C.Gram, H.Brauner-Osborne, K.Madsen, L.B.Knudsen, and B.S.Wulff (2003).
Three distinct epitopes on the extracellular face of the glucagon receptor determine specificity for the glucagon amino terminus.
  J Biol Chem, 278, 28005-28010.  
12370417 C.Fernández, C.Hilty, G.Wider, and K.Wüthrich (2002).
Lipid-protein interactions in DHPC micelles containing the integral membrane protein OmpX investigated by NMR spectroscopy.
  Proc Natl Acad Sci U S A, 99, 13533-13537.  
12491536 C.G.Unson (2002).
Molecular determinants of glucagon receptor signaling.
  Biopolymers, 66, 218-235.  
11226244 C.Fernández, K.Adeishvili, and K.Wüthrich (2001).
Transverse relaxation-optimized NMR spectroscopy with the outer membrane protein OmpX in dihexanoyl phosphatidylcholine micelles.
  Proc Natl Acad Sci U S A, 98, 2358-2363.
PDB code: 1orm
11470082 P.A.Luchette, T.N.Vetman, R.S.Prosser, R.E.Hancock, M.P.Nieh, C.J.Glinka, S.Krueger, and J.Katsaras (2001).
Morphology of fast-tumbling bicelles: a small angle neutron scattering and NMR study.
  Biochim Biophys Acta, 1513, 83-94.  
10727928 B.C.Chia, J.A.Carver, T.D.Mulhern, and J.H.Bowie (2000).
Maculatin 1.1, an anti-microbial peptide from the Australian tree frog, Litoria genimaculata solution structure and biological activity.
  Eur J Biochem, 267, 1894-1908.  
10681555 M.Beyermann, S.Rothemund, N.Heinrich, K.Fechner, J.Furkert, M.Dathe, R.Winter, E.Krause, and M.Bienert (2000).
A role for a helical connector between two receptor binding sites of a long-chain peptide hormone.
  J Biol Chem, 275, 5702-5709.  
10447695 A.Haouz, S.El Mohsni, C.Zentz, F.Merola, and B.Alpert (1999).
Heterogeneous motions within human apohemoglobin.
  Eur J Biochem, 264, 250-257.  
10590300 R.M.Epand, and H.J.Vogel (1999).
Diversity of antimicrobial peptides and their mechanisms of action.
  Biochim Biophys Acta, 1462, 11-28.  
10479738 X.Gao, and T.C.Wong (1999).
The study of the conformation and interaction of two tachykinin peptides in membrane mimicking systems by NMR spectroscopy and pulsed field gradient diffusion.
  Biopolymers, 50, 555-568.  
9836590 K.A.Carpenter, and P.W.Schiller (1998).
Aggregation behaviour and Zn2+ binding properties of secretin.
  Biochemistry, 37, 16967-16974.  
9657683 K.L.Brown, S.Cheng, X.Zou, J.Li, G.Chen, E.J.Valente, J.D.Zubkowski, and H.M.Marques (1998).
Structural and enzymatic studies of a new analogue of coenzyme B12 with an alpha-adenosyl upper axial ligand.
  Biochemistry, 37, 9704-9715.  
9927994 V.Wray, K.Nokihara, and S.Naruse (1998).
Solution structure comparison of the VIP/PACAP family of peptides by NMR spectroscopy.
  Ann N Y Acad Sci, 865, 37-44.  
9235002 A.L.Lomize, and H.I.Mosberg (1997).
Thermodynamic model of secondary structure for alpha-helical peptides and proteins.
  Biopolymers, 42, 239-269.  
8785330 D.A.Keire, and T.G.Fletcher (1996).
The conformation of substance P in lipid environments.
  Biophys J, 70, 1716-1727.  
8619998 P.K.Hammen, D.G.Gorenstein, and H.Weiner (1996).
Amphiphilicity determines binding properties of three mitochondrial presequences to lipid surfaces.
  Biochemistry, 35, 3772-3781.  
8634236 W.Blankenfeldt, K.Nokihara, S.Naruse, U.Lessel, D.Schomburg, and V.Wray (1996).
NMR spectroscopic evidence that helodermin, unlike other members of the secretin/VIP family of peptides, is substantially structured in water.
  Biochemistry, 35, 5955-5962.  
7592863 M.R.Tota, L.Xu, A.Sirotina, C.D.Strader, and M.P.Graziano (1995).
Interaction of [fluorescein-Trp25]glucagon with the human glucagon receptor expressed in Drosophila Schneider 2 cells.
  J Biol Chem, 270, 26466-26472.  
7893948 R.M.Campbell, J.Bongers, and A.M.Felix (1995).
Rational design, synthesis, and biological evaluation of novel growth hormone releasing factor analogues.
  Biopolymers, 37, 67-88.  
8143730 J.F.O'Connell, R.Bender, J.W.Engels, K.P.Koller, M.Scharf, and K.Wüthrich (1994).
The nuclear-magnetic-resonance solution structure of the mutant alpha-amylase inhibitor [R19L] Tendamistat and comparison with wild-type Tendamistat.
  Eur J Biochem, 220, 763-770.  
  1304373 M.Shoemaker, P.C.Lin, and B.Haley (1992).
Identification of the guanine binding domain peptide of the GTP-binding site of glucagon.
  Protein Sci, 1, 884-891.  
1726781 B.Bechinger, Y.Kim, L.E.Chirlian, J.Gesell, J.M.Neumann, M.Montal, J.Tomich, M.Zasloff, and S.J.Opella (1991).
Orientations of amphipathic helical peptides in membrane bilayers determined by solid-state NMR spectroscopy.
  J Biomol NMR, 1, 167-173.  
1841698 J.E.Mertz, P.Güntert, K.Wüthrich, and W.Braun (1991).
Complete relaxation matrix refinement of NMR structures of proteins using analytically calculated dihedral angle derivatives of NOE intensities.
  J Biomol NMR, 1, 257-269.  
2001694 T.Maurer, C.Lücke, and H.Rüterjans (1991).
Investigation of the membrane-active peptides melittin and glucagon by photochemically induced dynamic-nuclear-polarization (photo-CIDNP) NMR.
  Eur J Biochem, 196, 135-141.  
1863695 Y.Theriault, Y.Boulanger, and S.St-Pierre (1991).
Structural determination of the vasoactive intestinal peptide by two-dimensional H-NMR spectroscopy.
  Biopolymers, 31, 459-464.  
2188279 D.M.LeMaster (1990).
Deuterium labelling in NMR structural analysis of larger proteins.
  Q Rev Biophys, 23, 133-174.  
2146114 H.Inooka, T.Kikuchi, S.Endo, Y.Ishibashi, M.Wakimasu, and E.Mizuta (1990).
Conformation in solution of porcine brain natriuretic peptide determined by combined use of nuclear magnetic resonance and distance geometry.
  Eur J Biochem, 193, 127-134.  
2091027 Y.Kim, and J.H.Prestegard (1990).
Refinement of the NMR structures for acyl carrier protein with scalar coupling data.
  Proteins, 8, 377-385.
PDB code: 1acp
  2676353 G.M.Clore, and A.M.Gronenborn (1989).
Determination of three-dimensional structures of proteins and nucleic acids in solution by nuclear magnetic resonance spectroscopy.
  Crit Rev Biochem Mol Biol, 24, 479-564.  
2598942 M.Hofmann, D.Gondol, G.Bovermann, and M.Nilges (1989).
Conformation of secretin in dimethyl sulfoxide solution. NMR studies and restrained molecular dynamics.
  Eur J Biochem, 186, 95.  
2585001 M.Sanner, A.Widmer, H.Senn, and W.Braun (1989).
GEOM: a new tool for molecular modelling based on distance geometry calculations with NMR data.
  J Comput Aided Mol Des, 3, 195-210.  
2730944 S.C.Lee, and A.F.Russell (1989).
Two-dimensional 1H-NMR study of the 1-34 fragment of human parathyroid hormone.
  Biopolymers, 28, 1115-1127.  
2831051 G.M.Clore, M.Nilges, A.Brünger, and A.M.Gronenborn (1988).
Determination of the backbone conformation of secretin by restrained molecular dynamics on the basis of interproton distance data.
  Eur J Biochem, 171, 479-484.  
3047742 J.de Vlieg, R.M.Scheek, W.F.van Gunsteren, H.J.Berendsen, R.Kaptein, and J.Thomason (1988).
Combined procedure of distance geometry and restrained molecular dynamics techniques for protein structure determination from nuclear magnetic resonance data: application to the DNA binding domain of lac repressor from Escherichia coli.
  Proteins, 3, 209-218.  
3186691 P.R.Gooley, S.A.Carter, P.E.Fagerness, and N.E.MacKenzie (1988).
Preferred conformational state of the N-terminus section of a bovine growth hormone fragment (residues 96-133) in water is an omega loop.
  Proteins, 4, 48-55.  
3282504 R.M.Cooke, and I.D.Campbell (1988).
Protein structure determination by nuclear magnetic resonance.
  Bioessays, 8, 52-56.  
3345756 W.E.Steinmetz, P.E.Bougis, H.Rochat, O.D.Redwine, W.Braun, and K.Wüthrich (1988).
1H nuclear-magnetic-resonance studies of the three-dimensional structure of the cardiotoxin CTXIIb from Naja mossambica mossambica in aqueous solution and comparison with the crystal structures of homologous toxins.
  Eur J Biochem, 172, 101-116.  
3149201 Y.Theriault, Y.Boulanger, and J.K.Saunders (1988).
Secondary structure of the human growth hormone releasing factor (GRF 1-29) by two-dimensional 1H-nmr spectroscopy.
  Biopolymers, 27, 1897-1904.  
2448843 D.J.Patel, L.Shapiro, and D.Hare (1987).
DNA and RNA: NMR studies of conformations and dynamics in solution.
  Q Rev Biophys, 20, 35.  
3447178 P.J.Kraulis, and T.A.Jones (1987).
Determination of three-dimensional protein structures from nuclear magnetic resonance data using fragments of known structures.
  Proteins, 2, 188-201.  
3310077 W.Braun (1987).
Distance geometry and related methods for protein structure determination from NMR data.
  Q Rev Biophys, 19, 115-157.  
3459158 A.T.Brünger, G.M.Clore, A.M.Gronenborn, and M.Karplus (1986).
Three-dimensional structure of proteins determined by molecular dynamics with interproton distance restraints: application to crambin.
  Proc Natl Acad Sci U S A, 83, 3801-3805.  
2425859 D.Gondol, and G.van Binst (1986).
Distance determination by a two-dimensional NOE NMR study on the medium-sized peptide gramicidin S.
  Biopolymers, 25, 977-983.  
2417837 G.Chassaing, O.Convert, and S.Lavielle (1986).
Preferential conformation of substance P in solution.
  Eur J Biochem, 154, 77-85.  
2453052 M.Waks (1986).
Proteins and peptides in water-restricted environments.
  Proteins, 1, 4.  
2992961 D.Neuhaus, G.Wagner, M.Vasák, J.H.Kägi, and K.Wüthrich (1985).
Systematic application of high-resolution, phase-sensitive two-dimensional 1H-NMR techniques for the identification of the amino-acid-proton spin systems in proteins. Rabbit metallothionein-2.
  Eur J Biochem, 151, 257-273.  
2992954 G.M.Clore, A.M.Gronenborn, and L.W.McLaughlin (1985).
The structure of the double-stranded RNA pentamer 5'(CACAG) . 5'(CUGUG) determined by nuclear Overhauser enhancement measurements: interproton distance determination and structure refinement on the basis of X-ray coordinates.
  Eur J Biochem, 151, 153-165.  
  3891324 G.M.Clore, and A.M.Gronenborn (1985).
The solution structure of a B-DNA undecamer comprising a portion of the specific target site for the cAMP receptor protein in the gal operon. Refinement on the basis of interproton distance data.
  EMBO J, 4, 829-835.  
6499847 A.M.Gronenborn, G.M.Clore, L.Hobbs, and J.Jeffery (1984).
Glucose-6-phosphate dehydrogenase. A transferred nuclear Overhauser enhancement study of NADP+ conformations in enzyme-coenzyme binary complexes.
  Eur J Biochem, 145, 365-371.  
6198174 A.Pardi, G.Wagner, and K.Wüthrich (1983).
Protein conformation and proton nuclear-magnetic-resonance chemical shifts.
  Eur J Biochem, 137, 445-454.  
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 code is shown on the right.