title: Activation of prothrombin by two subtilisin-like serine proteases from Acremonium sp.
abstract: Two novel subtilisin-like serine proteases (AS-E1 and -E2) that activate prothrombin have been identified in a culture of the fungus Acremonium sp. The enzymes were purified through repeated hydrophobic interaction chromatography. The N-terminal sequences of AS-E1 (34.4 kDa) and AS-E2 (32 kDa) showed high similarity to the internal sequences of two distinct subtilisin-like hypothetical proteins from Chaetomium globosum. Both enzymes proteolytically activated prothrombin to meizothrombin(desF1)-like molecules, while the activation cleavage seemed to occur at a site (Tyr(316)-Ile(317)) that is four residues proximal to the canonical Xa cleavage site (Arg(320)-Ile(321)). Both enzymes inhibited plasma clotting, possibly due to extensive degradation of fibrinogen and production of meizothrombin(desF1)-like molecule.
authors.affiliation: Department of Applied Biological Science, Tokyo Noko University, 3-5-8 Saiwaicho, Fuchu-shi, Tokyo 183-8509, Japan.
authors.forename: Chunli
authors.initials: C
authors.lastname: Liu
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Matsushita
authors.forename: Kosuke
authors.initials: K
authors.lastname: Shimizu
authors.forename: Koichi
authors.initials: K
authors.lastname: Makimura
authors.forename: Keiji
authors.initials: K
authors.lastname: Hasumi
mesh_terms: D000164:Acremonium / Q000201:enzymology; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D002597:Chaetomium / Q000201:enzymology; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D005656:Fungal Proteins / Q000302:isolation & purification / Q000378:metabolism*; D011516:Prothrombin / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D013917:Thrombin / Q000378:metabolism*
chemical_list: D004792:Enzyme Precursors; D005656:Fungal Proteins; D011516:Prothrombin; D012697:Serine Endopeptidases; D013917:Thrombin; C026812:meizothrombin