Catalytic domains of the human hepatocyte growth factor receptor tyrosine kinase and methods for identification of inhibitors thereof

• Main Authors: ZHU, JEFF, PARGE, HANS, SARUP, JAY, MCTIGUE, MICHELE ANN, HICKEY, MICHAEL, MURRAY, BRION WILLIAM, MROCZKOWSKI, BARBARA
• Format: Patent
• Language: English; French; German
• Published: 12.02.2003
• Edition: 7
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS OR TEST PAPERS THEREFOR; COMPOSITIONS THEREOF; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL ORENZYMOLOGICAL PROCESSES; CULTURE MEDIA; ENZYMOLOGY; FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE; MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEICACIDS OR MICROORGANISMS; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PROCESSES OF PREPARING SUCH COMPOSITIONS; PROCESSES USING MICROORGANISMS; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPIRITS; VINEGAR; WINE

The identification, isolation, purification, and characterization of the catalytic domain of the human hepatocyte growth factor receptor kinase (hHGFR) are described. A crystal structure of the hHGFR kinase domain is reported herein. This structure provides a three-dimensional description of the binding site of the hHGFR for structure-based design of small molecule inhibitors thereof as therapeutic agents. The kinase domain of human HGFR and its associated crystal structure is described for use in the discovery, identification and characeterization of modulators of human HGFR.