2asu
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(New page: 200px<br /> <applet load="2asu" size="450" color="white" frame="true" align="right" spinBox="true" caption="2asu, resolution 1.85Å" /> '''Crystal Structure o...)
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Revision as of 18:48, 12 November 2007
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Crystal Structure of the beta-chain of HGFl/MSP
Overview
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.
About this Structure
2ASU is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the beta-chain of human hepatocyte growth factor-like/macrophage stimulating protein., Carafoli F, Chirgadze DY, Blundell TL, Gherardi E, FEBS J. 2005 Nov;272(22):5799-807. PMID:16279944
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