%0 Journal Article
%T Genetic Basis for Variation of Metalloproteinase-Associated Biochemical Activity in Venom of the Mojave Rattlesnake (Crotalus scutulatus scutulatus)
%A Ruben K. Dagda
%A Sardar Gasanov
%A Ysidro De La OIII
%A Eppie D. Rael
%A Carl S. Lieb
%J Biochemistry Research International
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/251474
%X The metalloproteinase composition and biochemical profiles of rattlesnake venom can be highly variable among rattlesnakes of the same species. We have previously shown that the neurotoxic properties of the Mojave rattlesnake (Crotalus scutulatus scutulatus) are associated with the presence of the Mojave toxin A subunit suggesting the existence of a genetic basis for rattlesnake venom composition. In this report, we hypothesized the existence of a genetic basis for intraspecies variation in metalloproteinase-associated biochemical properties of rattlesnake venom of the Mojave rattlesnake. To address this question, we PCR-amplified and compared the genomic DNA nucleotide sequences that code for the mature metalloproteinase domain of fourteen Mojave rattlesnakes captured from different geographical locations across the southwest region of the United States. In addition, the venoms from the same rattlesnakes were tested for their ability to hydrolyze fibrinogen, fibrin, casein, and hide powder azure and for induction of hemorrhage in mice. Overall, based on genomic sequencing and biochemical data, we classified Mojave rattlesnake venom into four distinct groups of metalloproteinases. These findings indicate that differences in nucleotide sequences encoding the mature proteinase domain and noncoding regions contribute to differences in venom metalloproteinase activities among rattlesnakes of the same species. 1. Introduction Rattlesnake venom metalloproteinases are zinc-dependent enzymes that hydrolyze fibrin and fibrinogen, inactivate complement proteins, and promote hemorrhage in vivo [1¨C4]. In addition, rattlesnake venom metalloproteinases show differences in substrate specificity, proteolytic activity, molecular weight, and composition of structural domains [5, 6]. Rattlesnake venom metalloproteinases are members of the Reprolysin superfamily of metalloproteinases [7]. These venom enzymes have been subcategorized into four classes (P-I to P-IV) based on the differences in structural domains, molecular weight, and biochemical properties [7, 8]. The P-I group of rattlesnake venom metalloproteinases contains a proteinase domain, whereas the P-II group contains an additional disintegrin-like domain. The P-III group has an additional disintegrin-like domain and cysteine-rich sequence, whereas the P-IV group has an additional lectin-like sequence [8]. The P-II and P-III classes of rattlesnake venom metalloproteinases are one- to twofold more potent at inducing hemorrhage than the P-I metalloproteinases [8¨C11]. This observation suggests that the
%U http://www.hindawi.com/journals/bri/2013/251474/