Ecarin
| Ecarin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 3.4.24.- | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| |||||||||
Ecarin is an metalloprotease enzyme[1] that is derived from the venom of the Indian saw-scaled viper, Echis carinatus,[2] It is the primary reagent in the Ecarin clotting time test.
Ecarin is known to activate prothrombin, another protein that is a critical component of the blood clotting cascade.[3]
Origin
[edit]
The venom of the saw-scaled viper, Echis carinatus, causes bleeding and eventually death.[4] The venom contains ecarin, which converts prothrombin to meizothrombin, a thrombin analog with increased esterase activity, and not to normal thrombin.[5]
Clinical Use
[edit]Ecarin is a highly versatile drug compound used in blood clotting experiments and for monitoring and treating a range of diseases, including cancer, liver diseases, lupus, and cardiovascular disorders.[6]
Testing
[edit]Ecarin-based assays are tests that have the prospect to be clinically helpful in detecting vitamin K deficiency and lupus anticoagulant. The Ecarin clotting time (ECT) is a test that is widely used for lupus anticoagulant testing in certain regions. Ecarin-based testing is used to monitor dabigatran etexilate,[7] a thrombin inhibitor,[8] with both clot-based and chromogenic-based methods available.[7]
In 2015, it was reported that 30% of oral anticoagulants prescribed for Medicare patients in the United States were direct oral anticoagulants (DOACs),[9] with dabigatran being a popular choice among cardiologists and internal medicine physicians. This is largely due to the drug's safety and efficacy. It has been shown to be effective in preventing stroke and systemic embolism, and has a lower risk of bleeding compared to warfarin. However, it is important to note that monitoring the effects of dabigatran can be challenging, as traditional coagulation tests such as the prothrombin time (PT) and activated partial thromboplastin time (aPTT) are not sensitive to the drug's effects. This is where Ecarin-based testing comes in, as it provides a more accurate measure of dabigatran's anticoagulant effect.[7]
Research
[edit]Ecarin is a glycoprotein with unique metalloproteinase properties. It has a molecular weight of 56,000 and has been found to specifically activate only prothrombin due to its strict substrate specificity. To compare the covalent structures of Ecarin and RVV-X, researchers have determined the complete cDNA sequence and translated protein sequence of Ecarin.[10]
References
[edit]- ^ Pötzsch B, Hund S, Madlener K, Unkrig C, Müller-Berghaus G (June 1997). "Monitoring of recombinant hirudin: assessment of a plasma-based ecarin clotting time assay". Thromb. Res. 86 (5): 373–83. doi:10.1016/S0049-3848(97)00082-0. PMID 9211628.
- ^ Ecarin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- ^ Jonebring, Anna; Lange, Ute; Bucha, Elke; Deinum, Johanna; Elg, Margareta; Lövgren, Ann (June 2012). "Expression and characterization of recombinant ecarin". The Protein Journal. 31 (5): 353–358. doi:10.1007/s10930-012-9409-6. ISSN 1875-8355. PMC 3380252. PMID 22528138.
- ^ Patra, Aparup; Kalita, Bhargab; Chanda, Abhishek; et al. (7 December 2017). "Proteomics and antivenomics of Echis carinatus carinatus venom: Correlation with pharmacological properties and pathophysiology of envenomation". Sci Rep. 7 (1) 17119. Bibcode:2017NatSR...717119P. doi:10.1038/s41598-017-17227-y. PMC 5719401. PMID 29215036.
- ^ Paine, Mark J. I.; Laing, Gavin D. (2013-01-01), Rawlings, Neil D.; Salvesen, Guy (eds.), "Chapter 240 - Ecarin", Handbook of Proteolytic Enzymes (Third Edition), Academic Press, pp. 1064–1067, doi:10.1016/b978-0-12-382219-2.00240-4, ISBN 978-0-12-382219-2, retrieved 2023-10-05
- ^ Mohammadi, Nasrin; Bandehpour, Mojgan; Sotoodehnejadnematalahi, Fattah; Kazemi, Bahram (March 2022). "Prokaryotic expression, evaluation, and prediction of the structure and function of the ecarin metalloproteinase domain". Proteins: Structure, Function, and Bioinformatics. 90 (3): 802–809. doi:10.1002/prot.26275. ISSN 0887-3585. PMID 34739152. S2CID 243761342.
- ^ a b c Gosselin, Robert C.; Douxfils, Jonathan (July 2020). "Ecarin based coagulation testing". American Journal of Hematology. 95 (7): 863–869. doi:10.1002/ajh.25852. ISSN 0361-8609. PMID 32350907. S2CID 217549415.
- ^ Dabigatran at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- ^ Ziakas, Panayiotis; Kourbeti, Irene; Poulou, Loukia; et al. (7 June 2018). "Medicare part D prescribing for direct oral anticoagulants in the United States: Cost, use and the "rubber effect"". PLOS One. 13 (6): e0198674. Bibcode:2018PLoSO..1398674Z. doi:10.1371/journal.pone.0198674. PMC 5991647. PMID 29879194.
- ^ Nishida, Shinji; Fujita, Taizo; Kohno, Noriatsu; Atoda, Hideko; Morita, Takashi; Takeya, Hiroyuki; Kido, Isao; Paine, Mark J. I.; Kawabata, Shun-ichiro; Iwanaga, Sadaaki (1995-02-07). "cDNA cloning and deduced amino acid sequence of prothrombin activator (ecarin) from Kenyan Echis carinatus venom". Biochemistry. 34 (5): 1771–1778. doi:10.1021/bi00005a034. ISSN 0006-2960. PMID 7849037.