1s18 | pdb_00001s18
Structure and protein design of human apyrase
Structural highlights
Disease[CANT1_HUMAN] Desbuquois syndrome. The disease is caused by mutations affecting the gene represented in this entry. Function[CANT1_HUMAN] Calcium-dependent nucleotidase with a preference for UDP. The order of activity with different substrates is UDP > GDP > UTP > GTP. Has very low activity towards ADP and even lower activity towards ATP. Does not hydrolyze AMP and GMP. Involved in proteoglycan synthesis.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHematophagous 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 beta 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. Structure and protein design of a human platelet function inhibitor.,Dai J, Liu J, Deng Y, Smith TM, Lu M Cell. 2004 Mar 5;116(5):649-59. PMID:15006348[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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