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Heparin-binding domain PDB id
1bht
Jmol
Contents
Protein chains
176 a.a. *
Ligands
SO4 ×3
EPE ×2
Waters ×266
* Residue conservation analysis
PDB id:
1bht
Name: Heparin-binding domain
Title: Nk1 fragment of human hepatocyte growth factor
Structure: Hepatocyte growth factor. Chain: a, b. Fragment: nk1 fragment, heparin binding domain plus c-met binding domain. Synonym: nk1. Engineered: yes. Other_details: hepes buffer molecule bound in kringle binding pocket
Source: Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: cytoplasm. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.00Å     R-factor:   0.196     R-free:   0.247
Authors: M.H.Ultsch,N.A.Lokker,P.J.Godowski,A.M.De Vos
Key ref:
M.Ultsch et al. (1998). Crystal structure of the NK1 fragment of human hepatocyte growth factor at 2.0 A resolution. Structure, 6, 1383-1393. PubMed id: 9817840 DOI: 10.1016/S0969-2126(98)00138-5
Date:
10-Jun-98     Release date:   04-Nov-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P14210  (HGF_HUMAN) -  Hepatocyte growth factor
Seq:
Struc: 		 
Seq:
Struc: 		728 a.a.
176 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1016/S0969-2126(98)00138-5 Structure 6:1383-1393 (1998)
PubMed id: 9817840  
 
 
Crystal structure of the NK1 fragment of human hepatocyte growth factor at 2.0 A resolution.
M.Ultsch, N.A.Lokker, P.J.Godowski, A.M.de Vos.
 
  ABSTRACT  
 
BACKGROUND: Hepatocyte growth factor (HGF) is a mitogen for hepatocytes and has also been implicated as an epithelial morphogen in tumor invasion. HGF activates its specific cellular receptor, c-met, through an aggregation mechanism potentiated by heparan sulfate glycosaminoglycans. HGF consists of an N-terminal (N) domain, four kringle domains (the first of which carries receptor-binding determinants), and an inactive serine-protease-like domain. NK1, a naturally occurring fragment of HGF, acts as an antagonist of HGF in the absence of heparin. RESULTS: The N domain of NK1 consists of a central five-stranded antiparallel beta sheet flanked by an alpha helix and a two-stranded beta ribbon. The overall N domain structure in the context of the NK1 fragment is similar to the structure of the isolated domain; two lysines and an arginine residue coordinate a bound sulfate ion. The NK1 kringle domain is homologous to kringle 4 from plasminogen, except that the lysine-binding pocket is altered by the insertion of a glycine residue. Here, a HEPES molecule is bound in the pocket. The asymmetric unit of the crystal contains a 'head-to-tail' NK1 dimer. We use this dimer to propose a model of the NK2 fragment of HGF. CONCLUSIONS: A cluster of exposed lysine and arginine residues in or near the hairpin-loop region of the N domain might form part of the NK1 heparin-binding site. In our NK2 model, both kringle domains pack loosely against the N domain, and a long, positively charged groove lines the interface. This groove might be involved in glycosaminoglycan binding. The HGF receptor-binding determinants are clustered near the binding pocket of the first kringle domain, opposite the N domain.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. Stereoview of the intramolecular interface between the N domain (green) and the kringle domain (yellow) around the salt bridge between Lys43 and Asp171. Water molecules are shown as red spheres, and hydrogen bonds are represented by dashed lines.
 
  The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 1383-1393) copyright 1998.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21199531 T.Nakamura, K.Sakai, T.Nakamura, and K.Matsumoto (2011).
Hepatocyte growth factor twenty years on: Much more than a growth factor.
  J Gastroenterol Hepatol, 26, 188-202.  
20050964 X.Yang, W.Cai, Z.Xu, J.Chen, C.Li, S.Liu, Z.Yang, Q.Pan, M.Li, J.Ma, and G.Gao (2010).
High efficacy and minimal peptide required for the anti-angiogenic and anti-hepatocarcinoma activities of plasminogen K5.
  J Cell Mol Med, 14, 2519-2530.  
16537482 E.Gherardi, S.Sandin, M.V.Petoukhov, J.Finch, M.E.Youles, L.G.Ofverstedt, R.N.Miguel, T.L.Blundell, G.F.Vande Woude, U.Skoglund, and D.I.Svergun (2006).
Structural basis of hepatocyte growth factor/scatter factor and MET signalling.
  Proc Natl Acad Sci U S A, 103, 4046-4051.
PDB codes: 2ced 2cee 2ceg 2cew
16403016 L.J.de Koning, P.T.Kasper, J.W.Back, M.A.Nessen, F.Vanrobaeys, J.Van Beeumen, E.Gherardi, C.G.de Koster, and L.de Jong (2006).
Computer-assisted mass spectrometric analysis of naturally occurring and artificially introduced cross-links in proteins and protein complexes.
  FEBS J, 273, 281-291.  
16129835 T.Bai, M.Becker, A.Gupta, P.Strike, V.J.Murphy, R.F.Anders, and A.H.Batchelor (2005).
Structure of AMA1 from Plasmodium falciparum reveals a clustering of polymorphisms that surround a conserved hydrophobic pocket.
  Proc Natl Acad Sci U S A, 102, 12736-12741.
PDB code: 1z40
15292253 M.Lyon, J.A.Deakin, D.Lietha, E.Gherardi, and J.T.Gallagher (2004).
The interactions of hepatocyte growth factor/scatter factor and its NK1 and NK2 variants with glycosaminoglycans using a modified gel mobility shift assay. Elucidation of the minimal size of binding and activatory oligosaccharides.
  J Biol Chem, 279, 43560-43567.  
15161915 T.G.Wright, J.Tsai, Z.Jia, and B.E.Elliott (2004).
Inhibition by copper(II) binding of hepatocyte growth factor (HGF) interaction with its receptor Met and blockade of HGF/Met function.
  J Biol Chem, 279, 32499-32506.  
14685170 C.Birchmeier, W.Birchmeier, E.Gherardi, and G.F.Vande Woude (2003).
Met, metastasis, motility and more.
  Nat Rev Mol Cell Biol, 4, 915-925.  
11876638 J.T.Douglas, P.D.von Haller, M.Gehrmann, M.Llinás, and J.Schaller (2002).
The two-domain NK1 fragment of plasminogen: folding, ligand binding, and thermal stability profile.
  Biochemistry, 41, 3302-3310.  
12372819 M.Peek, P.Moran, N.Mendoza, D.Wickramasinghe, and D.Kirchhofer (2002).
Unusual proteolytic activation of pro-hepatocyte growth factor by plasma kallikrein and coagulation factor XIa.
  J Biol Chem, 277, 47804-47809.  
11832492 P.Pediaditakis, S.P.Monga, W.M.Mars, and G.K.Michalopoulos (2002).
Differential mitogenic effects of single chain hepatocyte growth factor (HGF)/scatter factor and HGF/NK1 following cleavage by factor Xa.
  J Biol Chem, 277, 14109-14115.  
11597998 D.Lietha, D.Y.Chirgadze, B.Mulloy, T.L.Blundell, and E.Gherardi (2001).
Crystal structures of NK1-heparin complexes reveal the basis for NK1 activity and enable engineering of potent agonists of the MET receptor.
  EMBO J, 20, 5543-5555.
PDB codes: 1gmn 1gmo
11468390 E.G.Huizinga, A.Schouten, T.M.Connolly, J.Kroon, J.J.Sixma, and P.Gros (2001).
The structure of leech anti-platelet protein, an inhibitor of haemostasis.
  Acta Crystallogr D Biol Crystallogr, 57, 1071-1078.
PDB code: 1i8n
10688652 T.Otsuka, J.Jakubczak, W.Vieira, D.P.Bottaro, D.Breckenridge, W.J.Larochelle, and G.Merlino (2000).
Disassociation of met-mediated biological responses in vivo: the natural hepatocyte growth factor/scatter factor splice variant NK2 antagonizes growth but facilitates metastasis.
  Mol Cell Biol, 20, 2055-2065.  
11081636 Y.Shen, M.Naujokas, M.Park, and K.Ireton (2000).
InIB-dependent internalization of Listeria is mediated by the Met receptor tyrosine kinase.
  Cell, 103, 501-510.  
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 codes are shown on the right.