1s1d
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Hematophagous arthropods secrete a salivary apyrase that inhibits platelet | + | 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. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Liu, J.]] | [[Category: Liu, J.]] | ||
[[Category: Lu, M.]] | [[Category: Lu, M.]] | ||
| - | [[Category: Smith, T | + | [[Category: Smith, T M.]] |
[[Category: ACT]] | [[Category: ACT]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: nucleotide-binding motif]] | [[Category: nucleotide-binding motif]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:56:55 2008'' |
Revision as of 12:57, 21 February 2008
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Structure and protein design of human apyrase
Overview
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.
About this Structure
1S1D is a Single protein structure of sequence from Homo sapiens with , , , and as ligands. Active as Apyrase, with EC number 3.6.1.5 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 14:56:55 2008
Categories: Apyrase | Homo sapiens | Single protein | Dai, J. | Deng, Y. | Liu, J. | Lu, M. | Smith, T M. | ACT | CA | GP2 | SO4 | TRS | Adpase | Calcium-binding protein | Five-blade beta propeller | Nucleotide-binding motif
