Functional roles of the two distinct domains of halysase, a snake venom metalloprotease, to inhibit human platelet aggregation |
| |
Authors: | You Weon-Kyoo Jang Yoon-Jung Chung Kwang-Hoe Jeon Ok-Hee Kim Doo-Sik |
| |
Institution: | Cardiovascular Research Institute, Comprehensive Cancer Center, and Department of Anatomy, University of California, San Francisco, CA, USA. |
| |
Abstract: | Halysase, a hemorrhagic metalloprotease, has an apparent molecular weight of 66kDa and belongs to the class P-III snake venom metalloprotease. Class P-III snake venom metalloproteases have multifunctional domains including a protease domain and a disintegrin-like domain. Halysase was able to preferentially hydrolyze the alpha-chain of fibrinogen. Proteolytic activity of the enzyme was completely inhibited by metal chelating agents but not by other typical protease inhibitors. The enzyme principally cleaves X-Leu, X-Tyr, X-Phe, and X-Ala peptide bonds of the oxidized insulin B-chain. Halysase strongly suppresses collagen-induced human platelet aggregation in a dose-dependent manner. Apohalysase that is devoid of its metalloprotease activity was also able to inhibit the platelet aggregation to a certain extent. Experimental evidence clearly indicates that each of the two distinct domains of halysase, the metalloprotease and the disintegrin-like domains, plays its characteristic role to inhibit human platelet aggregation. |
| |
Keywords: | Hemorrhagic metalloprotease Snake venom Platelet aggregation Disintegrin-like domain Fibrinogen Collagen |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|