TAILIEUCHUNG - Báo cáo khoa học: Hepatocyte growth factor activator (HGFA): molecular structure and interactions with HGFA inhibitor-1 (HAI-1)

The trypsin-like serine protease hepatocyte growth factor activator (HGFA) undergoes proteolytic activation during blood coagulation, result-ing in a 34 kDa ‘short form’, consisting mainly of the protease domain. The crystal structures of the recombinantly expressed HGFA ‘short form’ discussed herein have provided molecular insights into its interaction with inhibitors and substrates, as well as the regulation of catalytic activity. | ỊFEBS Journal MINIREVIEW Hepatocyte growth factor activator HGFA molecular structure and interactions with HGFA inhibitor-1 HAI-1 Charles Eigenbrot1 2 Rajkumar Ganesan3 and Daniel Kirchhofer3 1 Department of StructuralBiology Genentech Inc. South San Francisco CA USA 2 Department of Antibody Engineering Genentech Inc. South San Francisco CA USA 3 Department of Protein Engineering Genentech Inc. South San Francisco CA USA Keywords catalysis hepatocyte growth factor Kunitz domain serine protease structure Correspondence D. Kirchhofer Genentech Inc. 1 DNA Way South San Francisco CA 94080 USA Fax 1 650 225-3734 Tel 1 650 225-2134 E-mail dak@ Received 13 November 2009 revised 19 January 2010 accepted 8 February 2010 doi The trypsin-like serine protease hepatocyte growth factor activator HGFA undergoes proteolytic activation during blood coagulation resulting in a 34 kDa short form consisting mainly of the protease domain. The crystal structures of the recombinantly expressed HGFA short form discussed herein have provided molecular insights into its interaction with inhibitors and substrates as well as the regulation of catalytic activity. The HGFA structures revealed enzymatically competent and noncompetent forms associated with the conformational states of two substrate specificity-determining loops the 220-loop and 99-loop. The implied dynamic behavior of these loops which are intimately involved in substrate interaction has precedents in other members of the S1 family of serine proteases and may be associated with specific mechanisms of enzyme regulation. Furthermore HGFA activity is strongly inhibited by HGFA inhibitor-1 a membrane-spanning multidomain inhibitor containing two Kunitz domains of which only the N-terminal Kunitz domain-1 KD1 inhibits enzymatic activity. In the structure of the KD1-HGFA complex the inhibitor interacts with the active site region by making contacts with all substrate specificity-determining loops

• Báo cáo khoa học
• Scientific reports
• scientific research
• molecular Biology
• Hepatocyte
• cytoplasm
• bacteria
• collection of scientific reports
• industry reports philosophy of history reports
• reports in literature
• a scientific b shirt
• presentation of scientific reports
• reports on literature
• philosophy statement
• documents
• studies English language and English language communication and English language commercial
• progress reports at scientific collections
• agronomic reports
• reports in physics
• biology reports
• thematic biological
• induced geometry
• mathematical topics
• quantum mechanics
• physics
• reporting mathematics
• physics reports
• livestock reports
• physical reports
• research physicist
• specializing in physics
• mathematical statements
• mathematical equations
• English pronunciation
• presentation report
• agricultural reports
• technical crops
• bio technology
• English reports
• presentation reports
• mathematical knowledge
• reports of mathematics
• represented
• Wilf on packing distinct
• Tur´n density
• mathematical works
• patterns in a permutation
• statements and documents scientific reports
• reports agronomy
• biotechnology
• plants Vietnam
• specialized biological
• microbiological methods
• presenting the report
• anti bacterial properties of shrimp
• energy exchange
• engineering chicken
• Path counting
• random matrix theory
• Even circuits
• prescribed clockwise parity
• Correspondence between
• algorithmic characterizations
• Finding Induced Acyclic
• Random Digraphs
• Nonexistence results
• Hadamard like matrices
• Voltage Graphs
• Group Presentations
• Cages mathematical knowledge
• Dominance Order
• Graphical Partitions
• On the functions
• values in [α(G
• Box With Translates
• Two Given Rectangular Brick
• On the q analogue
• the sum of cubes