title: cDNA sequences for four snake venom metalloproteinases: structure, classification, and their relationship to mammalian reproductive proteins.
abstract: Presented here are four new cDNA sequences for hemorrhagic metalloproteinases from Crotalus atrox venom, hemorrhagic toxins a, b, c, and d. Comparison of the translated open reading frames to the mature protein sequences gives evidence for post-translational processing at both the amino and carboxyl termini. This comparison is also the basis for a new classification system for these precursors, based on their different sizes. Protein sequences in the zymogen region support the hypothesis of a cysteine-switch type mechanism of maintaining latency. The coordination geometry around the active site zinc ion is discussed. The relationship between these venom metalloproteinases and a family of mammalian reproductive proteins is also supported by these sequences. The cysteine pattern of the carboxyl-terminal domain of the largest proteinase, hemorrhagic toxin a, is compared to other venom proteinases and to the mammalian proteins, showing both striking similarities and subtle differences. It would appear that these hemorrhagic toxins have resulted from deletions and subsequent divergence from a larger ancestor, one they may have shared with the aforementioned mammalian reproductive proteins.
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: L G
authors.initials: LG
authors.lastname: Jia
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; D017124:Conserved Sequence; D003435:Crotalid Venoms / Q000096:biosynthesis*; D018076:DNA, Complementary / Q000737:chemistry* / Q000378:metabolism; D015723:Gene Library; D008322:Mammals; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D009842:Oligopeptides / Q000032:analysis; D016366:Open Reading Frames; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D012911:Snakes
chemical_list: D003435:Crotalid Venoms; D018076:DNA, Complementary; D015345:Oligonucleotide Probes; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D008666:Metalloendopeptidases