title: Chemical modifications of PhTX-I myotoxin from Porthidium hyoprora snake venom: effects on structural, enzymatic, and pharmacological properties.
abstract: We recently described the isolation of a basic PLA2 (PhTX-I) from Porthidium hyoprora snake venom. This toxin exhibits high catalytic activity, induces in vivo myotoxicity, moderates footpad edema, and causes in vitro neuromuscular blockade. Here, we describe the chemical modifications of specific amino acid residues (His, Tyr, Lys, and Trp), performed in PhTX-I, to study their effects on the structural, enzymatic, and pharmacological properties of this myotoxin. After chemical treatment, a single His, 4 Tyr, 7 Lys, and one Trp residues were modified. The secondary structure of the protein remained unchanged as measured by circular dichroism; however other results indicated the critical role played by Lys and Tyr residues in myotoxic, neurotoxic activities and mainly in the cytotoxicity displayed by PhTX-I. His residue and therefore catalytic activity of PhTX-I are relevant for edematogenic, neurotoxic, and myotoxic effects, but not for its cytotoxic activity. This dissociation observed between enzymatic activity and some pharmacological effects suggests that other molecular regions distinct from the catalytic site may also play a role in the toxic activities exerted by this myotoxin. Our observations supported the hypothesis that both the catalytic sites as the hypothetical pharmacological sites are relevant to the pharmacological profile of PhTX-I.
authors.affiliation: Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, 13083-970 Campinas, SP, Brazil.
authors.forename: Salomón
authors.initials: S
authors.lastname: Huancahuire-Vega
authors.forename: Daniel H A
authors.initials: DH
authors.lastname: Corrêa
authors.forename: Luciana M
authors.initials: LM
authors.lastname: Hollanda
authors.forename: Marcelo
authors.initials: M
authors.lastname: Lancellotti
authors.forename: Carlos H I
authors.initials: CH
authors.lastname: Ramos
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: Ponce-Soto
authors.forename: Sergio
authors.initials: S
authors.lastname: Marangoni
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D020134:Catalytic Domain; D002460:Cell Line; D054501:Group II Phospholipases A2 / Q000737:chemistry* / Q000633:toxicity; D051379:Mice; D009498:Neurotoxins / Q000737:chemistry* / Q000633:toxicity; D017433:Protein Structure, Secondary; D030162:Reptilian Proteins / Q000737:chemistry* / Q000633:toxicity; D012910:Snake Venoms / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000596:Amino Acids; D009498:Neurotoxins; D030162:Reptilian Proteins; D012910:Snake Venoms; D054501:Group II Phospholipases A2