tailieunhanh - Báo cáo khoa học: Crystal structure of the b-chain of human hepatocyte growth factor-like ⁄macrophage stimulating protein

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. | ềFEBS Journal Crystal structure of the b-chain of human hepatocyte growth factor-like macrophage stimulating protein Federico Carafoli1 Dimitri Y. Chirgadze2 Tom L. Blundell2 and Ermanno Gherardi1 1 MRC Centre Hills Road Cambridge UK 2 Department of Biochemistry University of Cambridge UK Keywords HGF SF HGFl MSP plasminogen serine proteinases plasminogen-related growth factors Correspondence E. Gherardi MRC Centre Hills Road Cambridge CB2 2QH UK Fax 44 1223215308 Tel 44 1223215308 E-mail egherard@ Note On leave from the Department of ExperimentalMedicine University of Pavia Italy. Present affiliation Biophysics Section Blackett Laboratory ImperialCollege London UK Received 27 June 2005 revised 18 August 2005 accepted 14 September 2005 doi 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 b-chain of human HGFl MSP a serine proteinase homology domain containing the high-affinity binding site for the RON receptor. The structure describes at A resolution the region of the domain corresponding to the receptor binding site recently defined in the HGF SF b-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 .

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