title: Biochemical, functional, structural and phylogenetic studies on Intercro, a new isoform phospholipase A2 from Crotalus durissus terrificus snake venom.
abstract: Crotoxin is a neurotoxin from Crotalus durissus terrificus venom that shows immunomodulatory, anti-inflammatory, antimicrobial, antitumor and analgesic activities. Structurally, this toxin is a heterodimeric complex composed by a toxic basic PLA2 (Crotoxin B or CB) non-covalently linked to an atoxic non-enzymatic and acidic component (Crotapotin, Crotoxin A or CA). Several CA and CB isoforms have been isolated and characterized, showing that the crotoxin venom fraction is, in fact, a mixture of different molecules derived from the combination of distinct subunit isoforms. Intercro (IC) is a protein from the same snake venom which presents high similarity in primary structure to CB, indicating that it could be an another isoform of this toxin. In this work, we compare IC to the crotoxin complex (CA/CB) and/or CB in order to understand its functional aspects. The experiments with IC revealed that it is a new toxin with different biological activities from CB, keeping its catalytic activity but presenting low myotoxicity and absence of neurotoxic activity. The results also indicated that IC is structurally similar to CB isoforms, but probably it is not able to form a neurotoxic active complex with crotoxin A as observed for CB. Moreover, structural and phylogenetic data suggest that IC is a new toxin with possible toxic effects not related to the typical CB neurotoxin.
authors.affiliation: Departamento de Bioquímica e Imunologia, FMRP - USP, Ribeirão Preto, SP, Brazil.
authors.forename: Lara F
authors.initials: LF
authors.lastname: Vieira
authors.forename: Angelo J
authors.initials: AJ
authors.lastname: Magro
authors.forename: Carlos A H
authors.initials: CA
authors.lastname: Fernandes
authors.forename: Bibiana M
authors.initials: BM
authors.lastname: de Souza
authors.forename: Walter L G
authors.initials: WL
authors.lastname: Cavalcante
authors.forename: Mário S
authors.initials: MS
authors.lastname: Palma
authors.forename: José C
authors.initials: JC
authors.lastname: Rosa
authors.forename: André L
authors.initials: AL
authors.lastname: Fuly
authors.forename: Marcos R M
authors.initials: MR
authors.lastname: Fontes
authors.forename: Márcia
authors.initials: M
authors.lastname: Gallacci
authors.forename: Diana S
authors.initials: DS
authors.lastname: Butzke
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Calderon
authors.forename: Rodrigo G
authors.initials: RG
authors.lastname: Stábeli
authors.forename: José R
authors.initials: JR
authors.lastname: Giglio
authors.forename: Andreimar M
authors.initials: AM
authors.lastname: Soares
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003435:Crotalid Venoms / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017839:Crotalus; D008297:Male; D051379:Mice; D008958:Models, Molecular; D054467:Phospholipases A2 / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D010802:Phylogeny; D016415:Sequence Alignment; D012910:Snake Venoms / Q000378:metabolism
chemical_list: D003435:Crotalid Venoms; D012910:Snake Venoms; D054467:Phospholipases A2; C000588917:intercro protein, Crotalus durissus terrificus
keywords: CB isoforms; Crotalus durissus terrificus; Intercro; Oligomerization; Phospholipase A(2)