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

  1. Antonello Merlino1,
  2. Giovanna Avella1,
  3. Sonia Di Gaetano2,
  4. Angela Arciello3,
  5. Renata Piccoli3,4,
  6. Lelio Mazzarella1,2,
  7. Filomena Sica1,2,*

Article first published online: 2 DEC 2008

DOI: 10.1002/pro.6

Issue

Protein Science

Protein Science

Volume 18, Issue 1, pages 50–57, January 2009

Additional Information

How to Cite

Merlino, A., Avella, G., Di Gaetano, S., Arciello, A., Piccoli, R., Mazzarella, L. and Sica, F. (2009), Structural features for the mechanism of antitumor action of a dimeric human pancreatic ribonuclease variant. Protein Science, 18: 50–57. doi: 10.1002/pro.6

Author Information

  1. 1

    Dipartimento di Chimica, Università degli Studi di Napoli “Federico II”, Via Cintia, Napoli 80126, Italy

  2. 2

    Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, Napoli 80134, Italy

  3. 3

    Dipartimento di Biologia Strutturale e Funzionale, Università degli Studi di Napoli “Federico II”, Via Cintia, Napoli 80126, Italy

  4. 4

    Istituto Nazionale di Biostrutture e Biosistemi (INBB), Italy

*Dipartimento di Chimica, Università di Napoli “Federico II,” Complesso Universitario di Monte Sant' Angelo, Via Cintia, 80126 Napoli, Italy

Publication History

  1. Issue published online: 16 DEC 2008
  2. Article first published online: 2 DEC 2008
  3. Manuscript Accepted: 13 OCT 2008
  4. Manuscript Revised: 2 OCT 2008
  5. Manuscript Received: 18 JUL 2008

Funded by

  • Ministero dell'Istruzione, dell'Università e della Ricerca. Grant Numbers: FIRB RBNE03B8KK and, PRIN2007

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References

  • 1
    Matousek J ( 1973) The effect of bovine seminal ribonuclease (AS RNase) on cells of Crocker tumour in mice. Experientia 29: 858–859.
  • 2
    Soucek J, Pouckova P, Matousek J, Stockbauer P, Dostal J, Zadinova M ( 1996) Antitumor action of bovine seminal ribonuclease. Neoplasma 43: 335–340.
  • 3
    Wu Y, Mikulski SM, Ardelt W, Rybak SM, Youle RJ ( 1993) A cytotoxic ribonuclease. Study of the mechanism of onconase cytotoxicity. J Biol Chem 268: 10686–10693.
  • 4
    Deptala A, Halicka HD, Ardelt B, Ardelt W, Mikulski SM, Shogen K, Darzynkiewicz Z ( 1998) Potentiation of tumor necrosis factor induced apoptosis by onconase. Int J Oncol 13: 11–16.
  • 5
    Merlino A, Mazzarella L, Carannante A, Di Fiore A, Di Donato A, Notomista E, Sica F ( 2005) The importance of dynamic effects on the enzyme activity: X-ray structure and molecular dynamics of onconase mutants. J Biol Chem 280: 17953–17960.
  • 6
    Blackburn P, Moore S ( 1982.) Pancreatic ribonuclease. In: BoyerPD, editor. The enzymes. New York: Academic Press, pp 317–433.
  • 7
    Raines RT ( 1998) Ribonuclease A. Chem Rev 98: 1045–1065.
  • 8
    Makarov AA, Ilinskaya ON ( 2003) Cytotoxic ribonucleases: molecular weapons and their targets. FEBS Lett 540: 15–20.
  • 9
    Leland PA, Schultz LW, Kim BM, Raines RT ( 1998) Ribonuclease A variants with potent cytotoxic activity. Proc Natl Acad Sci USA 95: 10407–10412.
  • 10
    Leland PA, Staniszewski KE, Kim BM, Raines RT ( 2001) Endowing human pancreatic ribonuclease with toxicity for cancer cells. J Biol Chem 276: 43095–43102.
  • 11
    Gaur D, Swaminathan S, Batra JK ( 2001) Interaction of human pancreatic ribonuclease with human ribonuclease inhibitor. Generation of inhibitor-resistant cytotoxic variants. J Biol Chem 276: 24978–24984.
  • 12
    Boix E, Wu Y, Vasandani VM, Saxena SK, Ardelt W, Ladner J, Youle RJ ( 1996) Role of the N terminus in RNase A homologues: differences in catalytic activity, ribonuclease inhibitor interaction and cytotoxicity. J Mol Biol 257: 992–1007.
  • 13
    Piccoli R, Vescia S, Bridges SH, D'Alessio G ( 1990) The antitumor action of seminal ribonuclease tested with the plasmacytoma spleen colonization assay. Ital J Biochem 39: 242–249.
  • 14
    Cafaro V, De Lorenzo C, Piccoli R, Bracale A, Mastronicola MR, Di Donato A, D'Alessio G ( 1995) The antitumor action of seminal ribonuclease and its quaternary conformations. FEBS Lett 359: 31–34.
  • 15
    Mastronicola MR, Piccoli R, D'Alessio G ( 1995) Key extracellular and intracellular steps in the antitumor action of seminal ribonuclease. Eur J Biochem 230: 242–249.
  • 16
    Sica F, Di Fiore A, Merlino A, Mazzarella L ( 2004) Structure and stability of the non-covalent swapped dimer of bovine seminal ribonuclease: an enzyme tailored to evade ribonuclease protein inhibitor. J Biol Chem 279: 36753–36760.
  • 17
    Piccoli R, Tamburrini M, Piccialli G, Di Donato A, Parente A, D'Alessio G ( 1992) The dual-mode quaternary structure of seminal RNase. Proc Natl Acad Sci USA 89: 1870–1874.
  • 18
    Mazzarella L, Capasso S, Demasi D, Di Lorenzo G, Mattia CA, Zagari A ( 1993) Bovine seminal ribonuclease: structure at 1.9 Å resolution. Acta Crystallogr D 49: 389–402.
    Direct Link:
  • 19
    Berisio R, Sica F, De Lorenzo C, Di Fiore A, Piccoli R, Zagari A, Mazzarella L ( 2003) Crystal structure of the dimeric unswapped form of bovine seminal ribonuclease. FEBS Lett 554: 105–110.
  • 20
    Merlino A, Vitagliano L, Sica F, Zagari A, Mazzarella L ( 2004) Population shift versus induced fit: the case of bovine seminal ribonuclease swapping dimer. Biopolymers 73: 689–695.
    Direct Link:
  • 21
    Merlino A, Ercole C, Picone D, Pizzo E, Mazzarella L, Sica F ( 2008) The buried diversity of bovine seminal ribonuclease: shape and cytotoxicity of the swapped noncovalent form of the enzyme. J Mol Biol 376: 427–437.
  • 22
    Kim JS, Soucek J, Matousek J, Raines RT ( 1995) Structural basis for the biological activities of bovine seminal ribonuclease. J Biol Chem 270: 10525–10530.
  • 23
    Leland PA, Raines RT ( 2001) Cancer chemotherapy–ribonucleases to the rescue. Chem Biol 8: 405–413.
  • 24
    Sorrentino S, Libonati M ( 1994) Human pancreatic-type and nonpancreatic-type ribonucleases: a direct side-by-side comparison of their catalytic properties. Arch Biochem Biophys 312: 340–348.
  • 25
    Kover KE, Bruix M, Santoro J, Batta G, Laurents DV, Rico M ( 2008) The solution structure and dynamics of human pancreatic ribonuclease determined by NMR Spectroscopy provide insight into its remarkable biological activities and inhibition. J Mol Biol 379: 953–965.
  • 26
    Pous J, Canals A, Terzyan SS, Guasch A, Benito A, Ribo M, Vilanova M, Coll M ( 2000) Three-dimensional structure of a human pancreatic ribonuclease variant, a step forward in the design of cytotoxic ribonucleases. J Mol Biol 303: 49–60.
  • 27
    Pous J, Mallorqui-Fernandez G, Peracaula R, Terzyan SS, Futami J, Tada H, Yamada H, Seno M, de Llorens R, Gomis-Ruth FX, Coll M ( 2001) Three-dimensional structure of human RNase 1 delta N7 at 1.9 A resolution. Acta Crystallogr D Biol Crystallogr 57: 498–505.
    Direct Link:
  • 28
    Yamada H, Tamada T, Kosaka M, Miyata K, Fujiki S, Tano M, Moriya M, Yamanishi M, Honjo E, Tada H, Ino T, Yamaguchi H, Futami J, Seno M, Nomoto T, Hirata T, Yoshimura M, Kuroki R ( 2007) ‘Crystal lattice engineering,’ an approach to engineer protein crystal contacts by creating intermolecular symmetry: crystallization and structure determination of a mutant human RNase 1 with a hydrophobic interface of leucines. Protein Sci 16: 1389–1397.
    Direct Link:
  • 29
    Johnson RJ, McCoy JG, Bingman CA, Phillips GN, Jr, Raines RT ( 2007) Inhibition of human pancreatic ribonuclease by the human ribonuclease inhibitor protein. J Mol Biol 368: 434–449.
  • 30
    Canals A, Pous J, Guasch A, Benito A, Ribo M, Vilanova M, Coll M ( 2001) The structure of an engineered domain-swapped ribonuclease dimer and its implications for the evolution of proteins toward oligomerization. Structure 9: 967–976.
  • 31
    De Lorenzo C, Tedesco A, Terrazzano G, Cozzolino R, Laccetti P, Piccoli R, D'Alessio G ( 2004) A human, compact, fully functional anti-ErbB2 antibody as a novel antitumour agent. Br J Cancer 91: 1200–1204.
  • 32
    De Lorenzo C, Cozzolino R, Carpentieri A, Pucci P, Laccetti P, D'Alessio G ( 2005) Biological properties of a human compact anti-ErbB2 antibody. Carcinogenesis 26: 1890–1895.
  • 33
    Spalletti-Cernia D, Sorrentino R, Di Gaetano S, Piccoli R, Santoro M, D'Alessio G, Laccetti P, Vecchio G ( 2004) Highly selective toxic and proapoptotic effects of two dimeric ribonucleases on thyroid cancer cells compared to the effects of doxorubicin. Br J Cancer 90: 270–277.
  • 34
    Piccoli R, Di Gaetano S, De Lorenzo C, Grauso M, Monaco C, Spalletti-Cernia D, Laccetti P, Cinatl J, Matousek J, D'Alessio G ( 1999) A dimeric mutant of human pancreatic ribonuclease with selective cytotoxicity toward malignant cells. Proc Natl Acad Sci USA 96: 7768–7773.
  • 35
    Di Gaetano S, D'Alessio G, Piccoli R ( 2001) Second generation antitumour human RNase: significance of its structural and functional features for the mechanism of antitumour action. Biochem J 358: 241–247.
  • 36
    Sica F, Di Fiore A, Zagari A, Mazzarella L ( 2003) The unswapped chain of bovine seminal ribonuclease: crystal structure of the free and liganded monomeric derivative. Proteins 52: 263–271.
    Direct Link:
  • 37
    Berisio R, Lamzin VS, Sica F, Wilson KS, Zagari A, Mazzarella L ( 1999) Protein titration in the crystal state. J Mol Biol 292: 845–854.
  • 38
    Jones S, Marin A, Thornton JM ( 2000) Protein domain interfaces: characterization and comparison with oligomeric protein interfaces. Protein Eng 13: 77–82.
  • 39
    Lee FS, Shapiro R, Vallee BL ( 1989) Tight-binding inhibition of angiogenin and ribonuclease A by placental ribonuclease inhibitor. Biochemistry 28: 225–230.
  • 40
    Rodriguez M, Benito A, Ribo M, Vilanova M ( 2006) Characterization of the dimerization process of a domain-swapped dimeric variant of human pancreatic ribonuclease. FEBS J 273: 1166–1176.
    Direct Link:
  • 41
    Otwinowski Z, Minor W ( 1997) Processing of x-ray diffraction data collected in oscillation mode. Methods Enzymol 276: 307–326.
  • 42
    French GS, Wilson KS ( 1978) On the treatment of negative intensity observations. Acta Crystallogr Sect A 34: 517–525.
    Direct Link:
  • 43
    Navaza J ( 1994) AMoRe an automated package for molecular replacement. Acta Crystallogr Sect A 50: 157–163.
    Direct Link:
  • 44
    Brunger AT, Adams PD, Clore GM, DeLano WL, Gros P, Grosse-Kunstleve RW, Jiang JS, Kuszewski J, Nilges M, Pannu NS, Read RJ, Rice LM, Simonson T, Warren GL ( 1998) Crystallography & NMR system: a new software suite for macromolecular structure determination. Acta Crystallogr D Biol Crystallogr 54(Part 5): 905–921.
    Direct Link:
  • 45
    Jones TA, Bergdoll M, Kjeldgaard M O: a macromolecule modeling environment. In: BuggC, EalickS, editors. Crystallographic and modeling methods in molecular design. New York: Springer-Verlag; 1990. pp 189–199.
  • 46
    Laskowski RA, MacArthur MW, Moss MD, Thorton JM ( 1993) PROCHECK: a program to check the stereochemical quality of protein structure. J Appl Crystallogr 26: 283–291.
    Direct Link:
  • 47
    Hooft RW, Vriend G, Sander C, Abola EE ( 1996) Errors in protein structures. Nature 381: 272.
  • 48
    Brunger AT X-PLOR version 3.8. New Haven, CT: Department of Molecular Biophysics and Biochemistry, Yale University; 1996.
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