title: Relationship between the structure and the enzymatic activity of crotoxin complex and its phospholipase A2 subunit: an in silico approach.
abstract: Crotoxin, one of the major toxins of South American rattlesnake Crotalus durissus subspecies, is an heterodimeric complex composed of two distinct subunits: a basic phospholipase A(2) (PLA(2), CB) and an acidic nontoxic catalytically inactive protein, crotapotin (CA). It's well known that CB has a high enzymatic activity; however the molecular aspects that determine this fact remain unknown. In this study, an in silico approach was used to predict the CA structure by homology modeling, and the crotoxin structure by means of molecular docking. CA structure was built using the software Modeller taking Crotalus atrox PLA(2) (1PP2:R) as a template. Different criteria measured by Procheck, Verify 3D and ProSA were indicative of the reliability and the proper fold for the predicted structural model of CA. Then, a combination of this model and CB crystal structure was used to build the structure of crotoxin complex through rigid-body protein-protein docking. The crotoxin-3D model suggested that by means of hydrophobic and π-π stacking interactions, CA-Y24 and CA-F119 interact with CB-F24 and CB-F119, respectively. Those interactions could prevent the interfacial adsorption of the CB onto the lipid/water interface by blocking part of the interfacial binding surface of the PLA(2). This fact could explain the differences regarding to enzymatic activity between the crotoxin complex and CB. In addition, the crotoxin-3D model showed solvent-exposed regions of CA that could bind the receptor expressed in target cells.
authors.affiliation: Programa de Ofidismo/Escorpionismo, Universidad de Antioquia, A.A. 1226, Medellín, Colombia. andrespj20@yahoo.es
authors.forename: Jaime Andrés
authors.initials: JA
authors.lastname: Pereañez
authors.forename: Iván Dario
authors.initials: ID
authors.lastname: Gómez
authors.forename: Arley Camilo
authors.initials: AC
authors.lastname: Patiño
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D003198:Computer Simulation; D003439:Crotoxin / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines / Q000737:chemistry; D054467:Phospholipases A2 / Q000737:chemistry*; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry*; D016415:Sequence Alignment; D040681:Structural Homology, Protein
chemical_list: D010713:Phosphatidylcholines; D021122:Protein Subunits; D003439:Crotoxin; D054467:Phospholipases A2