Production of type II ribotoxins by Aspergillus species and related fungi in Taiwan

Lin, Alan; Huang, Kuan-Chun; Hwu, Luen; Tzean, S. S.

doi:10.1016/0041-0101(94)00140-4

Cited by 18 publications

(15 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This observation prompted the development of their molecular characterization (Lacadena et al, 2007). Much later, more systematic analysis of fungal genomes revealed that ribotoxins were a more widespread group of proteins within the filamentous fungi than had been previously believed (Lin et al, 1995;Martínez-Ruiz et al, 1999b;Varga and Samson, 2008). All this exhaustive work dealing with the characterization of their mechanism of action at the molecular level has not only helped to understand the basis of their antitumoral action (Lacadena et al, 2007) but also has established the principles to transform some of them into engineered chimeras with potential therapeutic uses (Carreras-Sangrà et al, 2008, 2012.…”

Section: Discussionmentioning

confidence: 99%

“…-Sarcin, restrictocin, and Aspf1 are the most exhaustively characterized ribotoxins (Arruda et al, 1992;García-Ortega et al, 2005;Gasset et al, 1994;Kao et al, 2001;Martínez-Ruiz et al, 2001;Wool, 1997), but many others have been identified and partially characterized within different fungal species (Huang et al,1997;Lin et al, 1995;Martínez-Ruiz et al, 1999a, 1999bParente et al, 1996;Varga and Samson, 2008;Wirth et al, 1997). These studies have shown a high degree of conservation among ribotoxins, as most of those so far characterized display amino acid sequence similarities above 85% (Lacadena et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Fungal extracellular ribotoxins as insecticidal agents

Olombrada¹,

Herrero-Galán²,

Tello³

et al. 2013

Insect Biochemistry and Molecular Biology

View full text Add to dashboard Cite

Fungal ribotoxins were discovered almost 50 years ago as extracellular ribonucleases (RNases) with antitumoral properties. However, the biological function of these toxic proteins has remained elusive. The discovery of the ribotoxin HtA, produced by the invertebrates pathogen H. thompsonii, revived the old proposal that insecticidal activity would be their long searched function. Unfortunately, HtA is rather singular among all ribotoxins known in terms of sequence and structure similarities. Thus, it was intriguing to answer the question of whether HtA is just an exception or, on the contrary, the paradigmatic example of the ribotoxins function. The work presented uses HtA and -sarcin, the most representative member of the ribotoxins family, to show their strong toxic action against insect larvae and cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fungal extracellular ribotoxins as insecticidal agents

Olombrada¹,

Herrero-Galán²,

Tello³

et al. 2013

Insect Biochemistry and Molecular Biology

View full text Add to dashboard Cite

show abstract

“…α-Sarcin, restrictocin, and Asp f 1 are the most exhaustively characterized ribotoxins [1][2][3][4][8][9][10], but many others have been identified and partially characterized in different fungal species [11][12][13][14][15][16], including the insecticidal protein hirsutellin A (HtA) produced by the invertebrate fungal pathogen Hirsutella thompsonii [15,17,18]. All ribotoxins show a high degree of amino acid sequence identity (above 85%) with precisely the only exception of HtA that displays only about 25% sequence identity with the previously known family members [15,18].…”

Section: Introductionmentioning

confidence: 99%

The Therapeutic Potential of Fungal Ribotoxins

Carreras-Sangrà

Álvarez-García²,

Herrero-Galán³

et al. 2008

CPB

View full text Add to dashboard Cite

Ribotoxins constitute a family of toxic extracellular fungal RNases that exert a highly specific activity on a conserved region of the larger molecule of rRNA, known as the sarcin-ricin loop. This cleavage of a single phosphodiester bond inactivates the ribosome and leads to protein synthesis inhibition and cell death. In addition to this ribonucleolytic activity, ribotoxins can cross lipid membranes in the absence of any known protein receptor. This ability is due to their capacity to interact with acid phospholipid-containing membranes. Both activities together explain their cytotoxic character, being rather specific when assayed against some transformed cell lines. The determination of highresolution structures of some ribotoxins, the characterization of a large number of mutants, and the use of lipid model vesicles and transformed cell lines have been the tools used for the study of their mechanism of action at the molecular level. The present knowledge suggests that wild-type ribotoxins or some modified variants might be used in human therapies. Production of hypoallergenic mutants and immunotoxins designed against specific tumors stand out as feasible alternatives to treat some human pathology in the midterm future.3

show abstract

“…Both primers were designed to introduce an EcoRI site (underlined nucleotides) for subcloning. The authentic ·-sarcin gene was first verified by hybridization with a synthetic oligo-DNA probe that carried a conserved sequence in fungal-originated ribosomeinactivating proteins [27]. The details of the coded sequence of the ·-sarcin gene were also determined by dideoxy chain-termination methods (Sequenase TM , version 2.0 kit, US Biochem.…”

Section: Construction Of the ·-Sarcin Gene And Its Mutants By Pcr Ampmentioning

confidence: 99%

The Action Mode of the Ribosome-Inactivating Protein α-Sarcin

Hwu¹,

Huang²,

Chen³

et al. 2000

J Biomed Sci

Self Cite

View full text Add to dashboard Cite

Based on the tertiary structure of the ribosome-inactivating protein α-sarcin, domains that are responsible for hydrolyzing ribosomes and naked RNA have been dissected. In this study, we found that the head-to-tail interaction between the first amino β-strand and the last carboxyl β-strand is not involved in catalyzing the hydrolysis of ribosomes or ribonucleic acids. Instead, a four-strand pleated β-sheet is indispensable for catalyzing both substrates, suggesting that α-sarcin and ribonuclease T1 (RNase T1) share a similar catalytic center. The integrity of an amino β-hairpin and that of the loop L3 in α-sarcin are crucial for recognizing and hydrolyzing ribosomes in vitro and in vivo. However, a mutant protein without the β-hairpin structure, or with a disrupted loop L3, is still capable of digesting ribonucleic acids. The functional involvement of the β-hairpin and the loop L3 in the sarcin stem/loop RNA of ribosomes is demonstrated by a docking model, suggesting that the two structures are in essence naturally designed to distinguish ribosome-inactivating proteins from RNase T1 to inactivate ribosomes.

show abstract

Production of type II ribotoxins by Aspergillus species and related fungi in Taiwan

Cited by 18 publications

References 23 publications

Fungal extracellular ribotoxins as insecticidal agents

Fungal extracellular ribotoxins as insecticidal agents

The Therapeutic Potential of Fungal Ribotoxins

The Action Mode of the Ribosome-Inactivating Protein α-Sarcin

Contact Info

Product

Resources

About

Production of type II ribotoxins by Aspergillus species and related fungi in Taiwan

Cited by 18 publications

References 23 publications

Fungal extracellular ribotoxins as insecticidal agents

Fungal extracellular ribotoxins as insecticidal agents

The Therapeutic Potential of Fungal Ribotoxins

The Action Mode of the Ribosome-Inactivating Protein &alpha;-Sarcin

Contact Info

Product

Resources

About

The Action Mode of the Ribosome-Inactivating Protein α-Sarcin