1S18

Structure and protein design of human apyrase

Summary for 1S18

• Entry DOI: 10.2210/pdb1s18/pdb
• Related: 1s1d
• Descriptor: apyrase, CALCIUM ION, ACETATE ION, ... (5 entities in total)
• Functional Keywords: adpase, five-blade beta propeller, calcium-binding protein, nucleotide-binding motif, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum membrane; Single-pass type II membrane protein: Q8WVQ1
• Total number of polymer chains: 2
• Total formula weight: 75255.69

Authors

Dai, J.,Liu, J.,Deng, Y.,Smith, T.M.,Lu, M. (deposition date: 2004-01-05, release date: 2004-03-16, Last modification date: 2024-02-14)

Primary citation

Dai, J.,Liu, J.,Deng, Y.,Smith, T.M.,Lu, M.
Structure and protein design of a human platelet function inhibitor.
Cell(Cambridge,Mass.), 116:649-659, 2004

PubMed 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 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.

PubMed: 15006348
DOI: 10.1016/S0092-8674(04)00172-2

Experimental method

X-RAY DIFFRACTION (1.7 Å)