title: Sequence of a cDNA clone encoding the zinc metalloproteinase hemorrhagic toxin e from Crotalus atrox: evidence for signal, zymogen, and disintegrin-like structures.
abstract: The sequence of two overlapping cDNA clones for the zinc metalloproteinase hemorrhagic toxin e (also known as atrolysin e, EC 3.4.24.44) from the venom gland of Crotalus atrox, the Western diamondback rattlesnake, is presented. The assembled cDNA sequence is 1975 nucleotides in length and encodes an open reading frame of 478 amino acids. The mature hemorrhagic toxin e protein as isolated from the crude venom has a molecular weight of approximately 24,000 and thus represents the processed product of this open reading frame. From the deduced amino acid sequence, it can be hypothesized that the enzyme is translated with a signal sequence of 18 amino acids, an amino-terminal propeptide of 169 amino acids, a central hemorrhagic proteinase domain of 202 amino acids, and a carboxy-terminal sequence of 89 amino acids. The propeptide has a short region similar to the region involved in the activation of matrix metalloproteinase zymogens. The proteinase domain is similar to other snake venom metalloproteinases, with over 57% identity to the low molecular weight proteinases HR2a and H2-proteinase from the Habu snake Trimeresurus flavoviridis. The carboxy-terminal region, which is not observed in the mature protein, strongly resembles the protein sequence immediately following the proteinase domain of HR1B (a high molecular weight hemorrhagic proteinase from the venom of T. flavoviridis) and the members of a different family of snake venom polypeptides known for their platelet aggregation inhibitory activity, the disintegrins. The cDNA sequence bears striking similarity to a previously reported sequence for a disintegrin cDNA. This report is evidence that this subfamily of venom metalloproteinases is synthesized in a proenzyme form which must be proteolytically activated.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Microbiology, University of Virginia Health Sciences Center, Charlottesville 22908.
authors.forename: L A
authors.initials: LA
authors.lastname: Hite
authors.forename: J D
authors.initials: JD
authors.lastname: Shannon
authors.forename: J B
authors.initials: JB
authors.lastname: Bjarnason
authors.forename: J W
authors.initials: JW
authors.lastname: Fox
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D003435:Crotalid Venoms / Q000235:genetics*; D004247:DNA / Q000235:genetics* / Q000302:isolation & purification; D004792:Enzyme Precursors / Q000235:genetics*; D015723:Gene Library; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics*; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D014176:Protein Biosynthesis; D021382:Protein Sorting Signals / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger; D012689:Sequence Homology, Nucleic Acid; D012911:Snakes / Q000235:genetics; D014757:Viper Venoms / Q000235:genetics*
chemical_list: D003435:Crotalid Venoms; D004792:Enzyme Precursors; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D014757:Viper Venoms; D011061:Poly A; D012313:RNA; D004247:DNA; D008666:Metalloendopeptidases; C044577:atrolysin A