PMID- 16279944
OWN - NLM
STAT- MEDLINE
DCOM- 20051230
LR  - 20210108
IS  - 1742-464X (Print)
IS  - 1742-464X (Linking)
VI  - 272
IP  - 22
DP  - 2005 Nov
TI  - Crystal structure of the beta-chain of human hepatocyte growth 
      factor-like/macrophage stimulating protein.
PG  - 5799-807
AB  - Hepatocyte growth factor like/macrophage stimulating protein (HGFl/MSP) and 
      hepatocyte growth factor/scatter factor (HGF/SF) define a distinct family of 
      vertebrate-specific growth factors structurally related to the blood proteinase 
      precursor plasminogen and with important roles in development and cancer. 
      Although the two proteins share a similar domain structure and mechanism of 
      activation, there are differences between HGFl/MSP and HGF/SF in terms of the 
      contribution of individual domains to receptor binding. Here we present a crystal 
      structure of the 30 kDa beta-chain of human HGFl/MSP, a serine proteinase 
      homology domain containing the high-affinity binding site for the RON receptor. 
      The structure describes at 1.85 Angstrom resolution the region of the domain 
      corresponding to the receptor binding site recently defined in the HGF/SF 
      beta-chain, namely the central cleft harboring the three residues corresponding 
      to the catalytic ones of active proteinases (numbers in brackets define the 
      sequence position according to the standard chymotrypsinogen numbering system) 
      [Gln522 (c57), Gln568 (c102) and Tyr661 (c195)] and an adjacent loop flanking the 
      S1 specificity pocket and containing residues Asn682 (c217) and Arg683 (c218) 
      previously shown to be essential for binding of HGFl/MSP to the RON receptor. The 
      study confirms the concept that the serine proteinase homology domains of 
      HGFl/MSP and HGF/SF bind their receptors in an 'enzyme-substrate' mode, 
      reflecting the common evolutionary origin of the plasminogen-related growth 
      factors and the proteinases of the clotting and fibrinolytic pathways. However, 
      analysis of the intermolecular interactions in the crystal lattice of beta-chain 
      HGFl/MSP fails to show the same contacts seen in the HGF/SF structures and does 
      not support a conserved mode of dimerization of the serine proteinase homology 
      domains of HGFl/MSP and HGF/SF responsible for receptor activation.
FAU - Carafoli, Federico
AU  - Carafoli F
AD  - MRC Centre, Hills Road, Cambridge, UK.
FAU - Chirgadze, Dimitri Y
AU  - Chirgadze DY
FAU - Blundell, Tom L
AU  - Blundell TL
FAU - Gherardi, Ermanno
AU  - Gherardi E
LA  - eng
SI  - PDB/2ASU
GR  - G9704528/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - 0 (HGF protein, human)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (RON protein)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - *Crystallography, X-Ray
MH  - Hepatocyte Growth Factor/*chemistry/genetics/*metabolism
MH  - Humans
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Mutation
MH  - Protein Binding
MH  - Protein Structure, Secondary
MH  - Protein Structure, Tertiary
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Spectrum Analysis, Raman
MH  - X-Ray Diffraction
EDAT- 2005/11/11 09:00
MHDA- 2005/12/31 09:00
CRDT- 2005/11/11 09:00
PHST- 2005/11/11 09:00 [pubmed]
PHST- 2005/12/31 09:00 [medline]
PHST- 2005/11/11 09:00 [entrez]
AID - EJB4968 [pii]
AID - 10.1111/j.1742-4658.2005.04968.x [doi]
PST - ppublish
SO  - FEBS J. 2005 Nov;272(22):5799-807. doi: 10.1111/j.1742-4658.2005.04968.x.