Ricin

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Ricin is a toxic protein found in castor oil plant seeds. The toxicity of Ricin has been known for centuries and was even used by the KGB government to assassinate Georgi Markov, a famous journalist who openly criticized the Soviet Union’s communist regime. The toxicity of ricin is caused by its ability to deactivate ribosomes and halt protein synthesis. Therefore, Ricin is categorized as a ribosome inactivating protein (RIP). There are two types of RIPs: type I and type II. Type I RIPs are usually heavily N-glycosylated and monomeric with a molecular weight around 30 kDa. Although they are capable of inactivating ribosomes, they are unable to transverse the cell membrane and make contact with the ribosomes, rendering them noncytoxic. Type II RIPs are heterodimeric toxins that contain an alpha and beta subunit connected by a disulfide bond between the cysteine residues near the C-terminus of the alpha subunit and the N-terminus of the beta subunit. The beta chain is shaped like a dumbbell, has 262 amino acids, and is a galactose/N-acetylgalactosamine-binding lectin that can bind to galactosidases on the cell surface. Once it has bound to a proteoglycan, the ricin protein is able to enter the cell via endocytosis. The alpha chain is an enzymatic polypeptide containing 267 amino acids with eight alpha helices (A-E) and eight beta sheets(a-e). It contains a binding site cleft that contains amino acids Tyr 80, Glu 177, Arg 180, Trp 211, and Tyr 123. The large ribosomal subunit binds to the binding cleft, where a specific adenine of the ribosomal subunit is sandwiched between Tyr 80 and Tyr 123. Arg 180 protonates the N-3 of adenine and breaks the bond between the the C-1’ of the ribose sugar and the N-9 of the adenine. Cleavage between the sugar and adenine base results in a oxycarbonium ion in the ribose that is stabilized by Glu 177. The protonation of N-3 causes deprotonation of a close by water molecule, causing it to act as a nucleophile and attack the...
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