Ribotoxic Proteins, Known as Inhibitors of Protein Synthesis, from Mushrooms and Other Fungi According to Endo’s Fragment Detection

Abstract

rRNA N-glycosylases (EC 3.2.2.22) remove a specific adenine (A4324, rat 28S rRNA) in the sarcin ricin loop (SRL) involved into ribosome interaction with elongation factors, causing the inhibition of translation, for which they are known as plant ‘ribosome inactivating proteins’ (RIPs). However, protein synthesis inactivation could be the result of other enzymes, which often have rRNA as the target. In this scenario, Endo’s assay is the most used method to detect the enzymes that are able to hydrolyze a phosphodiester bond or cleave a single N-glycosidic bond (rRNA N-glycosylases). Indeed, the detection of a diagnostic fragment from rRNA after enzymatic action, with or without acid aniline, allows one to discriminate between the N-glycosylases or hydrolases, which release the β-fragment after acid aniline treatment or α-fragment without acid aniline treatment, respectively. This assay is of great importance in the mushroom kingdom, considering the presence of enzymes that are able to hydrolyze phosphodiester bonds (e.g., ribonucleases, ribotoxins and ribotoxin-like proteins) or to remove a specific adenine (rRNA N-glycosylases). Thus, here we used the β-fragment experimentally detected by Endo’s assay as a hallmark to revise the literature available on enzymes from mushrooms and other fungi, whose action consists of protein biosynthesis inhibition.

Mushrooms as future generation healthy foods

“…The lectins found in some mushrooms have higher specificity for N-acetyl galactosamine and are known to possess antiviral and immune-stimulating properties to fight certain illnesses ( 145 ). Numerous lectins from mushrooms have shown potent inhibitory activity toward cancer cells through fungal extracellular ribonucleases acting as immunotoxins and are characterized by exerting their cellular cytotoxicity by inactivating ribosomes, leading to protein biosynthesis inhibition and death of neoplastic cells ( 146 , 147 ).…”

Streptavidin-Saporin: Converting Biotinylated Materials into Targeted Toxins

“…Saporin is an N-glycohydrolase and removes a single base in the rRNA, A4324. This eliminates the ability of the ribosome to perform protein synthesis [ 1 , 2 ]. Because of the lack of protein synthesis, any affected cell will die.…”

A Novel EGFR Targeted Immunotoxin Based on Cetuximab and Type 1 RIP Quinoin Overcomes the Cetuximab Resistance in Colorectal Cancer Cells

“…RIPs are N-β-glycosylases (EC 3.2.2.22) able to remove a single adenine from the 28S rRNA (A 4324 , rat liver numbering), highly conserved in Sarcin Ricin Loop (SRL), and involved in ribosome interaction with prokaryotic or eukaryotic elongation factors (EF-G or EF-2, respectively) [ 12 , 13 ]. The SRL and, thus, ribosomes damaged by this enzymatic action are unable to perform protein synthesis [ 14 ], promoting cell death by apoptotic pathway [ 15 ].…”

“…The SRL and, thus, ribosomes damaged by this enzymatic action are unable to perform protein synthesis [ 14 ], promoting cell death by apoptotic pathway [ 15 ]. RIPs are predominantly isolated from flowering plants (homologous proteins group [ 16 , 17 ]), although analogue enzymes able to inhibit protein synthesis are retrieved in fungi [ 12 ], bacteria [ 18 ] and one alga [ 19 ]. RIPs are classically divided into three groups due to the absence or presence of quaternary structure.…”