The cytotoxins alpha-sarcin and ricin retain their specificity when tested on a synthetic oligoribonucleotide (35-mer) that mimics a region of 28 S ribosomal ribonucleic acid.

Endo, Yaeta; Chan, Yuen‐Ling; Lin, Alan; Tsurugi, Kunio; Wool, Ira G.

doi:10.1016/s0021-9258(18)68418-2

Cited by 113 publications

(38 citation statements)

References 14 publications

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“…The branched side chain of this residue forms double hydrogen bonds with N1 and N2 of the guanine base and thereby discriminates guanine from adenine [34,36]. The lack of this residue in restrictocin could explain the observation that restrictocin is only purine-specific towards naked RNAs, rather than guanine-specific as for T1 and Sa [15].…”

Section: The Base Recognition Sitementioning

confidence: 99%

“…Extensive studies on substrate specificity have been carried out using a synthetic oligoribonucleotide (35-mer) that reproduces the conserved nucleotides, and presumably the secondary structure, of the ␣-sarcin domain of ribosomes [15]. To retain substrate specificity, a stem containing a minimum of three base pairs [16] and a guanine base, six bases 5′ to the cleavage site, were found to be essential [17].…”

Section: Introductionmentioning

confidence: 99%

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Insights into specificity of cleavage and mechanism of cell entry from the crystal structure of the highly specific Aspergillus ribotoxin, restrictocin

1996

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Restriction appears to combine the catalytic components of T1 ribonucleases with the base recognition components of Sa ribonucleases. Modeling studies using an NMR structure of an RNA substrate analog suggest that the tertiary structure of the substrate RNA is important in protein-RNA recognition, fitting closely into the concavity of the presumed binding site. We speculate that the large 39-residue loop L3, which has similarities to loops found in lectin sugar-binding domains, may be responsible for restrictocin's ability to cross cell membranes.

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Section: The Base Recognition Sitementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Insights into specificity of cleavage and mechanism of cell entry from the crystal structure of the highly specific Aspergillus ribotoxin, restrictocin

1996

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“…Throughout this paper we will refer to the S/R motif located in H95 of 23S rRNA from Haloarcula marismortui as the prototype, the sequence of which is indicated by the red rectangle in the upper row of Figure 2A . The H95 motif of bacterial 23S rRNA is sensitive to the toxins sarcin and ricin giving the motif its name ( 28 ).…”

Section: Resultsmentioning

confidence: 99%

Context-sensitivity of isosteric substitutions of non-Watson–Crick basepairs in recurrent RNA 3D motifs

Khisamutdinov

Sweeney

Leontis

2021

Nucleic Acids Research

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Sequence variation in a widespread, recurrent, structured RNA 3D motif, the Sarcin/Ricin (S/R), was studied to address three related questions: First, how do the stabilities of structured RNA 3D motifs, composed of non-Watson–Crick (non-WC) basepairs, compare to WC-paired helices of similar length and sequence? Second, what are the effects on the stabilities of such motifs of isosteric and non-isosteric base substitutions in the non-WC pairs? And third, is there selection for particular base combinations in non-WC basepairs, depending on the temperature regime to which an organism adapts? A survey of large and small subunit rRNAs from organisms adapted to different temperatures revealed the presence of systematic sequence variations at many non-WC paired sites of S/R motifs. UV melting analysis and enzymatic digestion assays of oligonucleotides containing the motif suggest that more stable motifs tend to be more rigid. We further found that the base substitutions at non-Watson–Crick pairing sites can significantly affect the thermodynamic stabilities of S/R motifs and these effects are highly context specific indicating the importance of base-stacking and base-phosphate interactions on motif stability. This study highlights the significance of non-canonical base pairs and their contributions to modulating the stability and flexibility of RNA molecules.

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“…Sequences of the 28S and 23S rRNA in α-SRL are highly conserved. Endo et al showed that ricin can retain its specificity mimic α-SRL on 35-mer synthetic oligoribonucleotide [ 40 ], which confirmed the importance of this loop on the depurination activity of RIPs.…”

Section: Trichosanthin As An Rrna N-glycosylasementioning

confidence: 91%

A Sixty-Year Research and Development of Trichosanthin, a Ribosome-Inactivating Protein

Lü

Wong

Shaw

2022

Toxins

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Tian Hua Fen, a herbal powder extract that contains trichosanthin (TCS), was used as an abortifacient in traditional Chinese medicine. In 1972, TCS was purified to alleviate the side effects. Because of its clinical applications, TCS became one of the most active research areas in the 1960s to the 1980s in China. These include obtaining the sequence information in the 1980s and the crystal structure in 1995. The replication block of TCS on human immunodeficiency virus in lymphocytes and macrophages was found in 1989 and started a new chapter of its development. Clinical studies were subsequently conducted. TCS was also found to have the potential for gastric and colorectal cancer treatment. Studies on its mechanism showed TCS acts as an rRNA N-glycosylase (EC 3.2.2.22) by hydrolyzing and depurinating A-4324 in α-sarcin/ricin loop on 28S rRNA of rat ribosome. Its interaction with acidic ribosomal stalk proteins was revealed in 2007, and its trafficking in mammalian cells was elucidated in the 2000s. The adverse drug reactions, such as inducing immune responses, short plasma half-life, and non-specificity, somehow became the obstacles to its usage. Immunotoxins, sequence modification, or coupling with polyethylene glycerol and dextran were developed to improve the pharmacological properties. TCS has nicely shown the scientific basis of traditional Chinese medicine and how its research and development have expanded the knowledge and applications of ribosome-inactivating proteins.

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The cytotoxins alpha-sarcin and ricin retain their specificity when tested on a synthetic oligoribonucleotide (35-mer) that mimics a region of 28 S ribosomal ribonucleic acid.

Cited by 113 publications

References 14 publications

Insights into specificity of cleavage and mechanism of cell entry from the crystal structure of the highly specific Aspergillus ribotoxin, restrictocin

Insights into specificity of cleavage and mechanism of cell entry from the crystal structure of the highly specific Aspergillus ribotoxin, restrictocin

Context-sensitivity of isosteric substitutions of non-Watson–Crick basepairs in recurrent RNA 3D motifs

A Sixty-Year Research and Development of Trichosanthin, a Ribosome-Inactivating Protein

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