Coding

Part:BBa_K4091024

Designed by: Ana Paula Contelli Xavier, Gabriel Kimijima Itaziki, Fabio Nigro Hoffman Leal, Jean Lucas Ribeiro.   Group: iGEM21_USP-EEL-Brazil   (2021-10-20)

Phospholipases are a superfamily of proteins that cleave phospholipids into lysophospholipids and fatty acids (SANTOS-FILHO, 2009). These enzymes act mainly in cell membranes and have, in general, optimal catalytic activity in the presence of calcium cations (SILVA, 2017). Depending on the classification of phospholipases, they can have various functions in different organisms. They can behave as digestive enzymes, and may also play an important role in cell membrane maintenance and remodeling, and also in cellular mechanisms regulation, such as the synthesis of bioactive lipid molecules. Being a large family of proteins, its variations are currently classified into 5 groups: the so-called secreted PLA2s (sPLA2), among them the PLA2s found in snake venom, the cytosolic PLA2s (cPLA2), the Ca2+ independent PLA2s (iPLA2), the acetylhydrolases, platelet-activating factors (PAF-AH) and the lysosomal PLA2s (SANTOS-FILHO, 2009).

This part is a PLA2 from Bothrops Jararaca and has a myotoxic function. Myotoxic phospholipases A2 disrupt the sarcolemma, the connective tissue that surrounds the muscle fiber, causing calcium ion influx and muscle necrosis. The tissue edema is multifactorial, due to the action of hemorrhagic metalloproteases, as well as catalytically active phospholipases A2 that play the role of inflammatory mediators production in localized edema, inducing mast cell exocytosis, releasing histamines, and producing bioactive lipids such as prostaglandins.

Phospholipases A2, in addition to generating necrosis of the muscle tissue where the inoculation occurred, end up damaging, in more severe cases, the kidneys causing several side effects to the body. After tissue death of the affected muscles, the cytoplasmic contents of the cells are released into the bloodstream, increasing the concentration of toxins called myoglobins, which are extremely harmful to the kidneys. (COSTA, 2017)

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Categories
//plasmid/expression
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