Part:BBa_K4091069

Snakes are naturally immune to their own venoms, and this also applies when it comes specifically to phospholipases A2. This is because of a natural protection consisting of inhibitors. These inhibitors have a molecular mass of 75 to 180 kDa and are formed by 3 to 6 subunits (some are glycosylated), equal or not, each with a mass of 20 to 50 kDa, linked in a non-covalent manner. Based on amino acid sequence homology, PLI's are divided into 3 classes, each with its different characteristic and spectrum of actions:

𝝰PLI's – They are globular proteins formed by 3 to 6 subunits, which can be 20 to 25 kDa in size. They are composed of 147 amino acids and an N-glycosylation site. Its main feature is the similar structure to the "carbohydrate recognition domain" (CRD) of Ca²+-dependent lectins, thus, possibly 𝝰PLI has its mechanism related to CRD, binding to the enzyme and inhibiting its catalytic activity. Current knowledge is that 𝝰PLI are more specific for group 2 acidic PLA2

βPLI - Acidic globular glycoproteins arranged in a protein homotrimer of 160 kDa, whose monomeric subunits are approximately 50 kDa. They are composed of 308 amino acids and 4 N-glycosylation sites per subunit. They are versatile structures, capable of forming a stable complex with PLA2. Their leucine-rich repeats enable a variety of protein interactions. It is currently described that its inhibition profile is restricted to PLA2s basic group II

𝛾PLI - These are composed of 3 to 6 subunits of 20 to 31 kDa joined by non-covalent bonds. As it is the most commonly found class in plasma, it became of greater interest to the project. Structurally, there is an intramolecular repetition of cysteine-rich domains, called three-finger. There is a subdivision within 𝛾PLI into heteromeric (I) and monomeric (II). They show a broad spectrum of action, being possible to inactivate PLA2 from different groups, with different isoelectric points. The hypothesis is that the three-finger domain are related to PLA inhibition.