Table 1.
Association rate constants (kapp × SI) and inhibition stoichiometries (SI)
Control antithrombin (β-antithrombin, S137A) and I207T and I207A variant reactions with FIIa and FXa. Values were measured as described under “Experimental procedures.” —, absence of cofactor; H5, pentasaccharide; UFH, unfractionated heparin; kapp, apparent second order rate constant for inhibition; SI, stoichiometry.
| kapp | SI | kapp × SI | |
|---|---|---|---|
| m−1 s−1 | |||
| FIIa | |||
| Control | |||
| — | (1.1 ± 0.2) × 104 | 1.2 ± 0.1 | (1.3 ± 0.2) × 104 |
| +UFH | (1.6 ± 0.1) × 107 | 1.7 ± 0.1 | (2.7 ± 0.3) × 107 |
| I207T | |||
| — | (3.8 ± 0.2) × 103 | 1.7 ± 0.1 | (6.5 ± 0.7) × 103 |
| +UFH | (4.9 ± 0.3) × 106 | 2.9 ± 0.0 | (1.4 ± 0.1) × 107 |
| I207A | |||
| — | (2.9 ± 0.9) × 102 | 94.2 ± 0.1 | (2.7 ± 0.8) × 104 |
| +UFH | (6.1 ± 0.8) × 104 | 242.3 ± 0.2 | (1.4 ± 0.2) × 107 |
| FXa | |||
| Control | |||
| — | (4.6 ± 0.4) × 103 | 1.1 ± 0.1 | (5.0 ± 0.1) × 103 |
| +H5 | (4.5 ± 0.5) × 105 | 1.5 ± 0.1 | (6.9 ± 1.2) × 105 |
| I207T | |||
| — | (2.8 ± 0.1) × 103 | 1.8 ± 0.1 | (5.0 ± 0.0) × 103 |
| +H5 | (2.5 ± 0.7) × 105 | 3.8 ± 0.2 | (9.5 ± 0.3) × 104 |
| I207A | |||
| — | (2.4 ± 0.5) × 102 | 160.0 ± 0.0 | (3.8 ± 0.8) × 104 |
| +H5 | (7.2 ± 0.7) × 103 | 471.8 ± 0.1 | (3.4 ± 0.3) × 106 |