2WPI
factor IXa superactive double mutant
Summary for 2WPI
Entry DOI | 10.2210/pdb2wpi/pdb |
Related | 1CFH 1CFI 1EDM 1IXA 1MGX 1NL0 1RFN 2WPH 2WPJ 2WPK 2WPL 2WPM |
Related PRD ID | PRD_001148 |
Descriptor | COAGULATION FACTOR IXA LIGHT CHAIN, D-PHE-PRO-ARG-CHLOROMETHYL KETONE, COAGULATION FACTOR IXA HEAVY CHAIN, ... (5 entities in total) |
Functional Keywords | blood clotting, hydrolase, glycoprotein, hemostasis |
Biological source | HOMO SAPIENS (HUMAN) More |
Cellular location | Secreted : P00740 P00740 |
Total number of polymer chains | 3 |
Total formula weight | 33056.64 |
Authors | Zogg, T.,Brandstetter, H. (deposition date: 2009-08-06, release date: 2009-12-22, Last modification date: 2024-11-20) |
Primary citation | Zogg, T.,Brandstetter, H. Structural Basis of the Cofactor- and Substrate-Assisted Activation of Human Coagulation Factor Ixa Structure, 17:1669-, 2009 Cited by PubMed Abstract: Human coagulation factor IX serves both to maintain and to control blood coagulation. The dual function of this hemophilic factor is implemented by a tiered activation mechanism. Processed two-chain factor IXa is catalytically silent; only together with its cofactor VIIIa does factor IXa form the highly potent Xase complex. The detailed mechanism of this secondary activation has remained elusive so far. Here we present the crystal structures of Xase-like factor IXa mutants with several-thousand-fold activity enhancement that mimic the secondary activation by Xase formation. The structures reveal how cofactor-triggered and substrate-assisted modulations in the factor IXa 99- and 60-loops cooperate in S4 through S2' formation, allowing for productive substrate recognition. We could further physically map and visualize a distinct communication line, along which agonists such as Ca(2+) direct their effects to the active site and vice versa. PubMed: 20004170DOI: 10.1016/J.STR.2009.10.011 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.99 Å) |
Structure validation
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