CDNA CLONING AND DEDUCED AMINO-ACID-SEQUENCE OF FIBRINOLYTIC ENZYME (LEBETASE) FROM VIPERA-LEBETINA SNAKE-VENOM

The complete amino acid sequence of lebetase is deduced from the nucle otide sequence of a cDNA clone isolated by screening a venomous gland c DNA library of Central Asian Vipera lebetina snake. The cDNA sequenc e with 2011 basepairs encodes an open reading frame of 478 amino acids which includes an 18 amino acid signal peptide, plus an 175 amino aci d segment of zymogen-like propeptide, a mature protein of 204 amino ac ids, a spacer of 18 amino acids and a disintegrin-like peptide of 63 a mino acids. The mature protein lebetase as isolated from the crude ven om has the molecular weight of approximately 23.7 kD and, thus, lebeta se as well as several other snake venom metalloproteinases is translat ed as a precursor protein, which may be processed posttranslationally. The lebetase proprotein has a ''cysteine switch'' motif(PKMCGV) simil ar to that involved in the activation of matrix metalloproteinase zymo gens. The mature protein (residues 223-427) shows the strongest simila rity with fibrolase(63% identity), fibrinolytic enzyme from Agkistrodo n contortrix contortrix venom. The metalloproteinase domain has a typi cal zinc-chelating sequence (HEXXHXXGXXH). In the disintegrin-like dom ain of protein, the RGD sequence is replaced by VGD. (C) 1996 Academic Press, Inc.