Human Pancreatic-Type and Nonpancreatic-Type Ribonucleases: A Direct Side-by-Side Comparison of Their Catalytic Properties

Sorrentino, Salvatore; Libonati, Massimo

doi:10.1006/abbi.1994.1318

Cited by 95 publications

(151 citation statements)

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“…Surprisingly, all the three RNases show several similarities despite structural and catalytic differences. All three RNase are pyrimidine specific, but RNase A shows a strong preference for polycytidylic acid and much less for polyuridylic acid (128) and onconase prefers polyuridylic acid (129). ZAG responds equally to polycytidylic acid and polyuridylic acid.…”

Section: Rnase Activitymentioning

confidence: 99%

Zinc α2-Glycoprotein: A Multidisciplinary Protein

Hassan

Waheed

Yadav

et al. 2008

Molecular Cancer Research

216

204

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Zinc A2-glycoprotein (ZAG) is a protein of interest because of its ability to play many important functions in the human body, including fertilization and lipid mobilization. After the discovery of this molecule, during the last 5 decades, various studies have been documented on its structure and functions, but still, it is considered as a protein with an unknown function. Its expression is regulated by glucocorticoids. Due to its high sequence homology with lipid-mobilizing factor and high expression in cancer cachexia, it is considered as a novel adipokine. On the other hand, structural organization and fold is similar to MHC class I antigen-presenting molecule; hence, ZAG may have a role in the expression of the immune response. The function of ZAG under physiologic and cancerous conditions remains mysterious but is considered as a tumor biomarker for various carcinomas. There are several unrelated functions that are attributed to ZAG, such as RNase activity, regulation of melanin production, hindering tumor proliferation, and transport of nephritic by-products. This article deals with the discussion of the major aspects of ZAG from its gene structure to function and metabolism. (Mol Cancer Res 2008;6(6):892 -906)

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Section: Rnase Activitymentioning

confidence: 99%

Zinc α2-Glycoprotein: A Multidisciplinary Protein

Hassan

Waheed

Yadav

et al. 2008

Molecular Cancer Research

216

204

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“…17 They differ for the swapping of the N-termini (residues 1-15) within a substantially identical quaternary framework. [18][19][20] In both isoforms, the dimeric interface is formed by the hinge peptides (residues [16][17][18][19][20][21][22] and the helices (residues [23][24][25][26][27][28][29][30][31][32][33][34] that comprise the four cysteines forming the two interchain disulfide bridges (Cys31-Cys32 0 and Cys32-Cys31 0 ) and the side chains of Leu28 and 28 0 that form stabilizing hydrophobic interactions across the molecular twofold axis. 18,20 In the most abundant swapped form, MxM-BSRNase, the dimeric interface also includes the closed interface arising from the swapped elements.…”

Section: Introductionmentioning

confidence: 99%

“…Compared with RNase A, it contains a higher percentage of basic residues, it shows a C-terminal extension of four residues (EDST) beyond the terminal valine (V124) and exhibits higher activity against double stranded RNA. 24 Up to now, all the attempts to grow crystals of the free native enzyme suitable for X-ray analysis failed; moreover, solution NMR studies have been hampered by aggregation problems. Only very recently, the solution structure of native HP-RNase has been reported (PDB code 2K11).…”

Section: Introductionmentioning

confidence: 99%

Structural features for the mechanism of antitumor action of a dimeric human pancreatic ribonuclease variant

et al. 2008

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A specialized class of RNases shows a high cytotoxicity toward tumor cell lines, which is critically dependent on their ability to reach the cytosol and to evade the action of the ribonuclease inhibitor (RI). The cytotoxicity and antitumor activity of bovine seminal ribonuclease (BSRNase), which exists in the native state as an equilibrium mixture of a swapped and an unswapped dimer, are peculiar properties of the swapped form. A dimeric variant (HHP2-RNase) of human pancreatic RNase, in which the enzyme has been engineered to reproduce the sequence of BSRNase helix-II (Gln28fiLeu, Arg31fiCys, Arg32fiCys, and Asn34fiLys) and to eliminate a negative charge on the surface (Glu111fiGly), is also extremely cytotoxic. Surprisingly, this activity is associated also to the unswapped form of the protein. The crystal structure reveals that on this molecule the hinge regions, which are highly disordered in the unswapped form of BSRNase, adopt a very well-defined conformation in both subunits. The results suggest that the two hinge peptides and the two Leu28 side chains may provide an anchorage to a transient noncovalent dimer, which maintains Cys31 and Cys32 of the two subunits in proximity, thus stabilizing a quaternary structure, similar to that found for the noncovalent swapped dimer of BSRNase, that allows the molecule to escape RI and/or to enhance the formation of the interchain disulfides.Keywords: crystal structure; antitumor agents; ribonuclease; 3D-domain swapping; dimers Abbreviations: BSRNase, bovine seminal ribonuclease; des(1-7)HP-RNase, human pancreatic ribonuclease in which the first seven residues have been deleted; HHP-RNase, covalent dimeric variant of human pancreatic ribonuclease in which four residues at the helix-II region are mutated according to BSRNase sequence (Gln28!Leu, Arg31!Cys, Arg32!Cys, and Asn34!Lys); HHP2-RNase, HHP-RNase with an additional mutation (Glu111!Gly); HP-RI, structure of human pancreatic ribonuclease complexed with ribonuclease inhibitor; HP-RNase, human pancreatic ribonuclease; MxM-BSRNase, dimeric form of BSRNase in which the chains swap their N-terminal tails; M¼M-BSRNase, unswapped dimer of BSRNase; M¼M-HHP2, unswapped dimer of HHP2-RNase; NCD-BSRNase, noncovalent swapped form of BSRNase; ONC, Onconase; PDB, Protein Data Bank; PM7, human pancreatic ribonuclease in which residues 1-21 are replaced by the corresponding residues of BSRNase; PM8, N-terminal swapped dimer of a variant of human pancreatic ribonuclease; RI, ribonuclease inhibitor; RMSD, root-mean-square deviation.Grant sponsor: Ministero dell'Istruzione, dell'Università e della Ricerca; Grant number: FIRB RBNE03B8KK and PRIN2007.

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“…However, it does show strong cleavage at 10UA and 6 UA, weak cleavage at 9UU and 5GU on the ssRNA, which is in accordance with the cleavage specificity of RNase A (Barnard 1969;Sorrentino and Libonati 1994).…”

Section: Chapter 2 -Investigation Of 3'rna Phosphodiesterase and 3 Exsupporting

confidence: 75%

“…Also, the identity of the two 10 nt products were shown to have resulted from the RNA endoribonuclease and 3'phosphodiesterase activities of WT APE1 cutting in between rUpA dinucleotides generating a 3 'phosphate and a 3 hydroxyl group product, respectively ( Figure 12B). In contrast, the RNase A marker which is known to possess only the endoribonuclease activity had no 3'RNA phosphodiesterase activity (Barnard 1969;Sorrentino and Libonati 1994).…”

Section: Assessing Known Inhibitors Of Ape1 Functions On 3 'Rna Phospmentioning

confidence: 98%

Investigating the 3' RNA Phosphodiesterase and 3'-5' Exoribonuclease Activities of APE1.

Chohan¹

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Human Pancreatic-Type and Nonpancreatic-Type Ribonucleases: A Direct Side-by-Side Comparison of Their Catalytic Properties

Cited by 95 publications

References 0 publications

Zinc α2-Glycoprotein: A Multidisciplinary Protein

Zinc α2-Glycoprotein: A Multidisciplinary Protein

Structural features for the mechanism of antitumor action of a dimeric human pancreatic ribonuclease variant

Investigating the 3' RNA Phosphodiesterase and 3'-5' Exoribonuclease Activities of APE1.

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