Antarease-like Zn-metalloproteases are ubiquitous in the venom of different scorpion genera |
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Authors: | Ernesto Ortiz,Martha Rendó n-Anaya,Solange Cristina Rego,Elisabeth Ferroni Schwartz,Lourival Domingos Possani |
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Affiliation: | 1. Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autonóma de México, Avenida Universidad 2001, Cuernavaca 62210, Mexico;2. Laboratorio Nacional de Genómica para la Biodiversidad, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Km 9.6 Libramiento Norte Carretera León, Irapuato, Guanajuato 36821, Mexico;3. Departamento de Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF 70910-900, Brazil |
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Abstract: | BackgroundThe venoms of several scorpion species have long been associated with pancreatitis in animal models and humans. Antarease, a Zn-metalloprotease from Tityus serrulatus, is able to penetrate intact pancreatic tissue and disrupts the normal vesicular traffic necessary for secretion, so it could play a relevant role in the onset of acute pancreatitis.MethodsThe cDNA libraries from five different scorpion species were screened for antarease homologs with specific primers. The amplified PCR products were cloned and sequenced. A structural model was constructed to assess the functionality of the putative metalloproteases. A phylogenetic analysis was performed to identify clustering patterns of these venom components.ResultsAntarease-like sequences were amplified from all the screened cDNA libraries. The complete sequence of the antarease from T. serrulatus was obtained. The structural model of the putative antarease from Tityus trivittatus shows that it may adopt a catalytically active conformation, sharing relevant structural elements with previously reported metalloproteases of the ADAM family. The phylogenetic analysis reveals that the reported sequences cluster in groups that correlate with the geographical localization of the respective species.ConclusionsAntareases are ubiquitous to a broad range of scorpion species, where they could be catalytically active enzymes. These molecules can be used to describe the evolution of scorpion venoms under different ecogeographic constrains.General significanceFor the first time the complete sequence of the antareases is reported. It is demonstrated that antareases are common in the venom of different scorpion species. They are now proposed as targets for antivenom therapies. |
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Keywords: | ADAM, a disintegrin and metalloproteinase BLAST, basic local alignment search tool HMM, hidden Markov model MD, molecular dynamics NPT, constant-temperature, constant-pressure ensemble PDB, protein data bank PSI-BLAST, position-specific iterative BLAST Rgyr, radius of gyration SVMP, snake venom protease, SNARE, soluble N-ethylmaleimide-sensitive factor attachment protein receptors TsTX, tityustoxin |
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