Biochemistry of frog ribonucleases

Irie, Masachika; Nitta, Kazuo; Nonaka, Takamasa

doi:10.1007/s000180050206

Cited by 65 publications

(71 citation statements)

References 42 publications

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“…Since the elucidation of the complete amino acid sequence of the Rana ribonuclease, Onconase, the relationship of this unusual protein to those of the more familiar RNase A superfamily ribonucleases has been in question. In the absence of a significant number of related sequences, Onconase and similar proteins from Rana catesbeiana and Rana japonica were initially included in a group that included the angiogenins (Irie et al 1998), based on the fact that both the Rana sequences and the angiogenins were missing cysteines at the canonical 4 th and 5 th positions (see Fig. 3B).…”

Section: Discussionmentioning

confidence: 99%

“…With respect to function in general, the Rana ribonucleases have been characterized as cytotoxins, but only in assays targeting mammalian tumor cell lines (Youle and D'Alessio 1997;Irie et al 1998). Though the pharmaceutical implications of this activity have yet to be fully realized, the physiologic implications are much less clear, as this toxicity may not be telling us much about the way in which Rana ribonucleases interact with cells and proteins present in Rana (as opposed to mammalian) species.…”

Section: Discussionmentioning

confidence: 99%

“…Also conserved is the B 1 binding site element phenylalanine-105, whereas histidine-104 and glutamate-98 of the B 2 binding site are somewhat (but not completely) conserved (Irie et al 1998).…”

Section: Identification Of Novel Ribonucleasementioning

confidence: 99%

“…Among the few nonmammalian members are the RNase A ribonucleases identified in several species of the bullfrog, genus Rana (Youle and D'Alessio 1997;Irie et al 1998). Among the earliest of this group to be identified was Onconase, a protein isolated from oocytes of the leopard frog, Rana pipiens, on the basis of its cytostatic, antineoplastic activity (Ardelt et al 1991).…”

Section: Introductionmentioning

confidence: 99%

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Rapid Diversification of RNase A Superfamily Ribonucleases from the Bullfrog, Rana catesbeiana

et al. 2001

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Abstract. We present sequences of five novel RNase A superfamily ribonuclease genes of the bullfrog, Rana catesbeiana. All five genes encode ribonucleases that are similar to Onconase, a cytotoxic ribonuclease isolated from oocytes of R. pipiens. With amino acid sequence data from 14 ribonucleases from three Rana species (R. catesbeiana, R. japonica, and R. pipiens), we have constructed bootstrap-supported phylogenetic trees that reorganize these ribonucleases into five distinct lineagesthe pancreatic ribonucleases (RNases 1), the eosinophilassociated ribonucleases (RNases 2, 3, and 6), the ribonucleases 4, the angiogenins (RNases 5) and the Rana ribonucleases-with the Rana ribonucleases no more closely related to the angiogenins than they are to any of the other ribonuclease lineages shown. Further phylogenetic analysis suggests the division of the Rana ribonucleases into two subclusters (A and B), with positive (Darwinian) selection (d N /d S > 1.0) and an elevated rate of radical nonsynonymous substitution (d R ) contributing to the rapid diversification of ribonucleases within each cluster. This pattern of evolution-rapid diversification via positive selection among sequences of a multigene cluster-bears striking resemblance to what we have described for the eosinophil-associated ribonuclease genes of the rodent Mus musculus, a finding that may have implications with respect the physiologic function of this unique family of proteins.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Identification Of Novel Ribonucleasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rapid Diversification of RNase A Superfamily Ribonucleases from the Bullfrog, Rana catesbeiana

et al. 2001

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“…There are six known human RNase A superfamily ribonucleases, including human pancreatic ribonuclease (RNase 1), the eosinophil ribonucleases (RNases 2 and 3), RNase 4, angiogenin (RNase 5), and RNase k6. Other distinctive family members include bovine seminal ribonuclease , a dimeric ribonuclease with selective toxicity for malignant cells, and onconase, an amphibian ribonuclease with similar cytotoxic properties (Youle and D'Alessio 1997; Irie et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Rapid Evolution of the Ribonuclease A Superfamily: Adaptive Expansion of Independent Gene Clusters in Rats and Mice

et al. 1999

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Abstract. The two eosinophil ribonucleases, eosinophil-derived neurotoxin (EDN/RNase 2) and eosinophil cationic protein (ECP/RNase 3), are among the most rapidly evolving coding sequences known among primates. The eight mouse genes identified as orthologs of EDN and ECP form a highly divergent, species-limited cluster. We present here the rat ribonuclease cluster, a group of eight distinct ribonuclease A superfamily genes that are more closely related to one another than they are to their murine counterparts. The existence of independent gene clusters suggests that numerous duplications and diversification events have occurred at these loci recently, sometime after the divergence of these two rodent species (∼10-15 million years ago). Nonsynonymous substitutions per site (d N ) calculated for the 64 mouse/rat gene pairs indicate that these ribonucleases are incorporating nonsilent mutations at accelerated rates, and comparisons of nonsynonymous to synonymous substitution (d N / d S ) suggest that diversity in the mouse ribonuclease cluster is promoted by positive (Darwinian) selection. Although the pressures promoting similar but clearly independent styles of rapid diversification among these primate and rodent genes remain uncertain, our recent findings regarding the function of human EDN suggest a role for these ribonucleases in antiviral host defense.

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Toward an antitumor form of bovine pancreatic ribonuclease: The crystal structure of three noncovalent dimeric mutants

et al. 2009

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The cytotoxic action of bovine seminal ribonuclease (BS-RNase) depends on its noncovalent swapped dimeric form (NCD-BS), which presents a compact structure that allows the molecule to escape ribonuclease inhibitor (RI). A key role in the acquisition of this structure has been attributed to the concomitant presence of a proline in position 19 and a leucine in position 28. The introduction of Leu28, Cys31, and Cys32 and, in addition, of Pro19 in the sequence of bovine pancreatic ribonuclease (RNase A) has produced two dimeric variants LCC and PLCC, which do exhibit a cytotoxic activity, though at a much lower level than BS-RNase. The crystal structure analysis of the noncovalent swapped form (NCD) of LCC and PLCC, complexed with the substrate analogue 2 '-deoxycytidylyl(3 ',5 ')-2 '-deoxyguanosine, has revealed that, differently from NCD-BS, the dimers adopt an opened quaternary structure, with the two Leu residues fully exposed to the solvent, that does not hinder the binding of RI. Similar results have been obtained for a third mutant of the pancreatic enzyme, engineered with the hinge peptide sequence of the seminal enzyme (residues 16-22) and the two cysteines in position 31 and 32, but lacking the hydrophobic Leu residue in position 28. The comparison of these three structures with those previously reported for other ribonuclease swapped dimers strongly suggests that, in addition to Pro19 and Leu28, the presence of a glycine at the N-terminal end of the hinge peptide is also important to push the swapped form of RNase A dimer into the compact quaternary organization observed for NCD-BS.

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Biochemistry of frog ribonucleases

Cited by 65 publications

References 42 publications

Rapid Diversification of RNase A Superfamily Ribonucleases from the Bullfrog, Rana catesbeiana

Rapid Diversification of RNase A Superfamily Ribonucleases from the Bullfrog, Rana catesbeiana

Rapid Evolution of the Ribonuclease A Superfamily: Adaptive Expansion of Independent Gene Clusters in Rats and Mice

Toward an antitumor form of bovine pancreatic ribonuclease: The crystal structure of three noncovalent dimeric mutants

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