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PDBsum entry 1sgf

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protein ligands metals Protein-protein interface(s) links
Growth factor PDB id
1sgf
Jmol
Contents
Protein chains
203 a.a. *
109 a.a. *
232 a.a. *
202 a.a. *
Ligands
NAG ×2
NAG-NAG
NDG-NAG
Metals
_ZN ×2
* Residue conservation analysis
PDB id:
1sgf
Name: Growth factor
Title: Crystal structure of 7s ngf: a complex of nerve growth facto four binding proteins (serine proteinases)
Structure: Nerve growth factor. Chain: a, x. Synonym: 7s ngf. Nerve growth factor. Chain: b, y. Synonym: 7s ngf. Nerve growth factor. Chain: g, z. Synonym: 7s ngf.
Source: Mus musculus. House mouse. Organism_taxid: 10090. Strain: swiss webster. Organ: male submandibular gland. Organ: male submandibular gland
Biol. unit: Hexamer (from PQS)
Resolution:
3.15Å     R-factor:   0.246     R-free:   0.282
Authors: B.D.V.Bax,T.L.Blundell,J.Murray-Rust,N.Q.Mcdonald
Key ref:
B.Bax et al. (1997). Structure of mouse 7S NGF: a complex of nerve growth factor with four binding proteins. Structure, 5, 1275-1285. PubMed id: 9351801 DOI: 10.1016/S0969-2126(97)00280-3
Date:
08-Aug-97     Release date:   27-May-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00757  (K1KB4_MOUSE) -  Kallikrein 1-related peptidase-like b4
Seq:
Struc:
256 a.a.
203 a.a.*
Protein chains
Pfam   ArchSchema ?
P01139  (NGF_MOUSE) -  Beta-nerve growth factor
Seq:
Struc:
241 a.a.
109 a.a.
Protein chains
Pfam   ArchSchema ?
P00756  (K1KB3_MOUSE) -  Kallikrein 1-related peptidase b3
Seq:
Struc:
261 a.a.
232 a.a.
Protein chain
Pfam   ArchSchema ?
P00757  (K1KB4_MOUSE) -  Kallikrein 1-related peptidase-like b4
Seq:
Struc:
256 a.a.
202 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains G, Z: E.C.3.4.21.35  - Tissue kallikrein.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage of Arg-|-Xaa bonds in small molecule substrates. Highly selective action to release kallidin (lysyl-bradykinin) from kininogen involves hydrolysis of Met-|-Xaa or Leu-|-Xaa. The rat enzyme is unusual in liberating bradykinin directly from autologous kininogens by cleavage at two Arg-|-Xaa bonds.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     intracellular signal transduction   2 terms 
  Biochemical function     catalytic activity     9 terms  

 

 
DOI no: 10.1016/S0969-2126(97)00280-3 Structure 5:1275-1285 (1997)
PubMed id: 9351801  
 
 
Structure of mouse 7S NGF: a complex of nerve growth factor with four binding proteins.
B.Bax, T.L.Blundell, J.Murray-Rust, N.Q.McDonald.
 
  ABSTRACT  
 
BACKGROUND: Nerve growth factor (NGF) is a neurotrophic factor that promotes the differentiation and survival of certain populations of neurons in the central and peripheral nervous systems. 7S NGF is an alpha 2 beta 2 gamma 2 complex in which the beta-NGF dimer (the active neurotrophin) is associated with two alpha-NGF and two gamma-NGF subunits, which belong to the glandular kallikrein family of serine proteinases. The gamma-NGF subunit is an active serine proteinase capable of processing the precursor form of beta-NGF, whereas alpha-NGF is an inactive serine proteinase. The structure of 7S NGF could be used as a starting point to design inhibitors that prevent NGF binding to its receptors, as a potential treatment of neurodegenerative diseases. RESULTS: The crystal structure of 7S NGF shows that the two gamma-NGF subunits make extensive interactions with each other around the twofold axis of the complex and have the C-terminal residues of the beta-NGF subunits bound within their active sites. The 'activation domain' of each of the alpha-NGF subunits is in an inactive (zymogen-like) conformation and makes extensive interactions with the beta-NGF dimer. The two zinc ions that stabilize the complex are located at the relatively small interfaces between the alpha-NGF and gamma-NGF subunits. CONCLUSIONS: The structure of 7S NGF shows how the twofold axis of the central beta-NGF dimer organizes the symmetry of this multisubunit growth factor complex. The extensive surface of beta-NGF buried within the 7S complex explains the lack of neurotrophic activity observed for 7S NGF. The regions of the beta-NGF dimer that contact the alpha-NGF subunits overlap with those known to engage NGF receptors. Two disulphide-linked loops on alpha-NGF make multiple interactions with beta-NGF and suggest that it might be possible to design peptides that inhibit the binding of beta-NGF to its receptors.
 
  Selected figure(s)  
 
Figure 7.
Figure 7. Electron density surrounding the zinc ion (off-white sphere) bound between the a1 and g1 subunits. The final 2F[o] -F[c] map is shown contoured at 1.5s (cyan) and 6s (off-white).
 
  The above figure is reprinted by permission from Cell Press: Structure (1997, 5, 1275-1285) copyright 1997.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20615447 P.Goettig, V.Magdolen, and H.Brandstetter (2010).
Natural and synthetic inhibitors of kallikrein-related peptidases (KLKs).
  Biochimie, 92, 1546-1567.  
18790733 A.Hoffmann, A.Funkner, P.Neumann, S.Juhnke, M.Walther, A.Schierhorn, U.Weininger, J.Balbach, G.Reuter, and M.T.Stubbs (2008).
Biophysical characterization of refolded Drosophila Spätzle, a cystine knot protein, reveals distinct properties of three isoforms.
  J Biol Chem, 283, 32598-32609.
PDB code: 3e07
  18678937 A.Hoffmann, P.Neumann, A.Schierhorn, and M.T.Stubbs (2008).
Crystallization of Spätzle, a cystine-knot protein involved in embryonic development and innate immunity in Drosophila melanogaster.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 707-710.  
16740631 M.Debela, V.Magdolen, N.Schechter, M.Valachova, F.Lottspeich, C.S.Craik, Y.Choe, W.Bode, and P.Goettig (2006).
Specificity profiling of seven human tissue kallikreins reveals individual subsite preferences.
  J Biol Chem, 281, 25678-25688.  
15651049 G.Laxmikanthan, S.I.Blaber, M.J.Bernett, I.A.Scarisbrick, M.A.Juliano, and M.Blaber (2005).
1.70 A X-ray structure of human apo kallikrein 1: structural changes upon peptide inhibitor/substrate binding.
  Proteins, 58, 802-814.
PDB code: 1spj
14974964 P.Muangman, L.A.Muffley, J.P.Anthony, M.L.Spenny, R.A.Underwood, J.E.Olerud, and N.S.Gibran (2004).
Nerve growth factor accelerates wound healing in diabetic mice.
  Wound Repair Regen, 12, 44-52.  
12668437 G.Settanni, A.Cattaneo, and P.Carloni (2003).
Molecular dynamics simulations of the NGF-TrkA domain 5 complex and comparison with biological data.
  Biophys J, 84, 2282-2292.  
12016211 F.X.Gomis-Rüth, A.Bayés, G.Sotiropoulou, G.Pampalakis, T.Tsetsenis, V.Villegas, F.X.Avilés, and M.Coll (2002).
The structure of human prokallikrein 6 reveals a novel activation mechanism for the kallikrein family.
  J Biol Chem, 277, 27273-27281.
PDB code: 1gvl
11863437 M.C.Hsieh, and B.S.Cooperman (2002).
Inhibition of prostate-specific antigen (PSA) by alpha(1)-antichymotrypsin: salt-dependent activation mediated by a conformational change.
  Biochemistry, 41, 2990-2997.  
11854276 T.Oka, T.Hakoshima, M.Itakura, S.Yamamori, M.Takahashi, Y.Hashimoto, S.Shiosaka, and K.Kato (2002).
Role of loop structures of neuropsin in the activity of serine protease and regulated secretion.
  J Biol Chem, 277, 14724-14730.  
12410565 Z.Zhu, J.Kleeff, H.Kayed, L.Wang, M.Korc, M.W.Büchler, and H.Friess (2002).
Nerve growth factor and enhancement of proliferation, invasion, and tumorigenicity of pancreatic cancer cells.
  Mol Carcinog, 35, 138-147.  
11283322 E.M.Shooter (2001).
Early days of the nerve growth factor proteins.
  Annu Rev Neurosci, 24, 601-629.  
10102985 H.Czapinska, and J.Otlewski (1999).
Structural and energetic determinants of the S1-site specificity in serine proteases.
  Eur J Biochem, 260, 571-595.  
  10595525 I.L.Shamovsky, G.M.Ross, R.J.Riopelle, and D.F.Weaver (1999).
The interaction of neurotrophins with the p75NTR common neurotrophin receptor: a comprehensive molecular modeling study.
  Protein Sci, 8, 2223-2233.  
9933620 T.Kishi, M.Kato, T.Shimizu, K.Kato, K.Matsumoto, S.Yoshida, S.Shiosaka, and T.Hakoshima (1999).
Crystal structure of neuropsin, a hippocampal protease involved in kindling epileptogenesis.
  J Biol Chem, 274, 4220-4224.
PDB code: 1npm
9726969 N.Beglova, L.LeSauteur, I.Ekiel, H.U.Saragovi, and K.Gehring (1998).
Solution structure and internal motion of a bioactive peptide derived from nerve growth factor.
  J Biol Chem, 273, 23652-23658.  
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.