FEATURES

FAMILY

DESCRIPTION

Also known as PA2H2_BOTMO, PA2H2. Snake venom phospholipase A2 (PLA2) homolog that lacks enzymatic activity. Shows high myotoxin activities (PubMed:9637370, PubMed:16442348). Also shows neurotoxicity, since it induces muscle paralysis when tested on mouse phrenic-diaphragm preparations (PubMed:16442348, PubMed:23810946, PubMed:26457430, PubMed:30679550). Displays edema-inducing activities (PubMed:9637370, PubMed:16442348, PubMed:26457430). Also displays antimicrobial activity against E.coli and C.albicans, as well as antitumoral activity against some human and mice cell lines (PubMed:16442348). In addition, it is effective as parasiticidal agent against Leishmania sp. and S.mansoni (PubMed:16442348). It also disrupts negatively charged liposomes in a dose- and temperature-dependent manner and shows toxicity by intraperitoneal route (PubMed:16442348). In contrast to other phospholipase A2-like toxins, this myotoxin does not require fatty acid binding to be active (PubMed:29287778). A model of myotoxic mechanism has been proposed: an apo Lys49-PLA2 is usually (but not here) activated by the entrance of a hydrophobic molecule (e.g. fatty acid) at the hydrophobic channel of the protein leading to a reorientation of a monomer (By similarity). This reorientation causes a transition between 'inactive' to 'active' states, causing alignment of C-terminal and membrane-docking sites (MDoS) side-by-side and putting the membrane-disruption sites (MDiS) in the same plane, exposed to solvent and in a symmetric position for both monomers (By similarity). The MDoS region stabilizes the toxin on membrane by the interaction of charged residues with phospholipid head groups (By similarity). Subsequently, the MDiS region destabilizes the membrane with penetration of hydrophobic residues (By similarity). This insertion causes a disorganization of the membrane, allowing an uncontrolled influx of ions (i.e. calcium and sodium), and eventually triggering irreversible intracellular alterations and cell death (By similarity). Homodimer; non-covalently linked (probable alternative/compact dimer conformation) (Ref.4, PubMed:26457430, PubMed:29287778, PubMed:30679550).

EXTERNAL LINKS

PA2H2

Basic phospholipase A2 homolog myotoxin II

PA2H2

Molecular Synopsis