Abstract
Hematophagous arthropods secrete a salivary apyrase that inhibits platelet activation by catabolizing ADP released from damaged tissues and blood cells. We report the X-ray crystal structures of a human enzyme of the soluble apyrase family in its apo state and bound to a substrate analog. The structures reveal a nucleotide binding domain comprising a five-blade β propeller, binding determinants of the substrate and the active site, and an unusual calcium binding site with a potential regulatory function. Using a comparative structural biology approach, we were able to redesign the human apyrase so as to enhance its ADPase activity by more than 100-fold. The engineered enzyme is a potent inhibitor of platelet aggregation and may serve as the basis for the development of a new class of antithrombotic agents.
Original language | English (US) |
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Pages (from-to) | 649-659 |
Number of pages | 11 |
Journal | Cell |
Volume | 116 |
Issue number | 5 |
DOIs | |
State | Published - Mar 5 2004 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- General Biochemistry, Genetics and Molecular Biology