EC Number   |
Protein Variants |
Reference |
|---|
   3.4.21.68 | F423A |
two chain form, site-directed mutagenesis |
651864 |
| 3.4.21.68 | F423A/R275E |
single-chain form, site-directed mutagenesis |
651864 |
| 3.4.21.68 | F423E |
two chain form, site-directed mutagenesis |
651864 |
| 3.4.21.68 | F423E/R275E |
single-chain form, site-directed mutagenesis |
651864 |
| 3.4.21.68 | K213A/H214A/R215A/R216A |
construction of a chimeric tissue plasminogen activator (t-PA) through kringle 2 domain removal and replacement of t-PA finger domain with the Vampire bat plasminogen activator one. Vampire bat plasminogen activator (b-PA) is a plasminogen activator with higher fibrin affinity and specificity in comparison to t-PA resulting in reduced probability of hemorrhage. b-PA is also resistant to plasminogen activator inhibitor-1 showing higher half-life compared to other variants of t-PA. The KHRR sequence at the initial part of protease domain is replaced by four alanine residues. The activity of therecombinant protein in the presence of fibrin is 1560 times more than its activity in the absence of fibrin, showing its higher specificity to fibrin. The chimeric enzyme shows 1.2fold higher fibrin binding in comparison to full-length enzyme |
731733 |
| 3.4.21.68 | L420A |
two chain form, site-directed mutagenesis |
651864 |
| 3.4.21.68 | L420A/R275E |
single-chain form, site-directed mutagenesis |
651864 |
| 3.4.21.68 | L420E |
two chain form, site-directed mutagenesis |
651864 |
| 3.4.21.68 | L420E/R275E |
single-chain form, site-directed mutagenesis |
651864 |
| 3.4.21.68 | more |
a much lower uptake clearance is found in the liver for lanoteplase compared to wild-type t-PA. Rate constants for cell surface binding, internalization, and degradation of lanoteplase are also lower than those for t-PA in primary cultured rat hepatocytes. Results suggest that the improved stability of lanoteplase in vivo is due to the delay in the receptor-mediated endocytosis of lanoteplase. Uptake clearance in liver decreases with coadministration of lactoferrin, a ligand for low-density lipoprotein receptor-related protein (LRP) and the asialoglycoprotein receptors (ASGP) and in Irpap1-/- mice, which have a hereditary deficiency of lipoprotein receptor-related protein. Uptake clearance is not affected by mannose, whereas that of t-PA decreases with both ligands and in Irpap1(-/-) mice. Hepatic disposition of lanoteplase seems to be mediated by common specific receptors for t-PA, including LRP and the ASGP receptors |
683402 |
