Functional roles of the two distinct domains of halysase, a snake venom metalloprotease, to inhibit human platelet aggregation.
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.
You
Weon-Kyoo
WK
Cardiovascular Research Institute, Comprehensive Cancer Center, and Department of Anatomy, University of California, San Francisco, CA, USA.
Jang
Yoon-Jung
YJ
Chung
Kwang-Hoe
KH
Jeon
Ok-Hee
OH
Kim
Doo-Sik
DS
D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D002478:Cells, Cultured; D003435:Crotalid Venoms; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008666:Metalloendopeptidases / Q000008:administration & dosage* / Q000737:chemistry*; D045726:Metalloproteases / Q000008:administration & dosage* / Q000737:chemistry*; D008969:Molecular Sequence Data; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000737:chemistry; D017434:Protein Structure, Tertiary; D012910:Snake Venoms / Q000008:administration & dosage* / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014757:Viper Venoms / Q000008:administration & dosage* / Q000737:chemistry*
D003435:Crotalid Venoms; D010975:Platelet Aggregation Inhibitors; D012910:Snake Venoms; D014757:Viper Venoms; D045726:Metalloproteases; D008666:Metalloendopeptidases; C508062:halysase, Gloydius halys