IUBMB Enzyme Nomenclature

EC 4.6.1.23

Accepted name: ribotoxin

Reaction: a 28S rRNA containing guanosine-adenosine pair + H2O = an [RNA fragment]-3'-adenosine-3'-phosphate + a 5'-a hydroxy-guanosine-3'-[RNA fragment] (overall reaction)
(1a) a 28S rRNA containing guanosine-adenosine pair = an [RNA fragment]-3'-adenosine-2',3'-cyclophosphate + a 5'-hydroxy-guanosine-3'-[RNA fragment]
(1b) an [RNA fragment]-3'-adenosine-2',3'-cyclophosphate + H2O = an [RNA fragment]-3'-adenosine-3'-phosphate

Other name(s): α-sarcin; rRNA endonuclease (ambiguous)

Systematic name: [28S-rRNA]-guanosine-adenosine 5'-hydroxy-guanosine-ribonucleotide-3'-[RNA fragment]-lyase (cyclicizing; [RNA fragment]-3'-adenosine-2',3'-cyclophosphate-forming and hydrolysing)

Comments: Ribotoxins are rRNA endonucleases that catalyse the cleavage of the phosphodiester bond between guanosine and adenosine residues at one specific position in 28S rRNA. The enzyme secreted by Aspergillus giganteus specifically cleaves rat 28S rRNA between G4325 and A4326 and displays cytotoxic activity toward animal cells. It can also act on bacterial rRNAs. The enzyme catalyses a two-stage endonucleolytic cleavage. The first reaction produces 5'-hydroxy-phosphooligonucletides and 3'-phosphooligonucleotides ending with 2',3'-cyclic phosphodiester, which are released from the enzyme. The enzyme then hydrolyses these cyclic compounds in a second reaction that takes place only when all the susceptible 3',5'-phosphodiester bonds have been cyclised. The second reaction is a reversal of the first reaction using the hydroxyl group of water instead of the 5'-hydroxyl group of ribose. The overall process is that of a phosphorus-oxygen lyase followed by hydrolysis to form the 3'-nucleotides.

References:

1. Chan, Y.L., Endo, Y. and Wool, I.G. The sequence of the nucleotides at the α-sarcin cleavage site in rat 28 S ribosomal ribonucleic acid. J. Biol. Chem 258 (1983) 12768-12770. [PMID: 6355092]

2. Lacadena, J., Martinez del Pozo, A., Lacadena, V., Martinez-Ruiz, A., Mancheno, J.M., Onaderra, M. and Gavilanes, J.G. The cytotoxin α-sarcin behaves as a cyclizing ribonuclease. FEBS Lett. 424 (1998) 46-48. [PMID: 9580156]

3. Citores, L., Iglesias, R., Ragucci, S., Di Maro, A. and Ferreras, J.M. Antifungal activity of α-sarcin against Penicillium digitatum: proposal of a new role for fungal ribotoxins. ACS Chem. Biol. 13 (2018) 1978-1982. [PMID: 29952541]

[EC 4.6.1.23 created 1992 as EC 3.1.27.10, transferred 2019 to EC 4.6.1.23]


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