1S18

Structure and protein design of human apyrase

1S18 の概要

• エントリーDOI: 10.2210/pdb1s18/pdb
• 関連するPDBエントリー: 1s1d
• 分子名称: apyrase, CALCIUM ION, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: adpase, five-blade beta propeller, calcium-binding protein, nucleotide-binding motif, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane; Single-pass type II membrane protein: Q8WVQ1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 75255.69

構造登録者

Dai, J.,Liu, J.,Deng, Y.,Smith, T.M.,Lu, M. (登録日: 2004-01-05, 公開日: 2004-03-16, 最終更新日: 2024-02-14)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.7 Å)