Structural and functional relationships of natural and artificial dimeric bovine ribonucleases: New scaffolds for potential antitumor drugs

FEBS Letters

Volumn 587, Issue 22, 2013, Pages 3601-3608

  Gotte, Giovanni ^a   Laurents, Douglas V ^b   Merlino, Antonello ^c   Picone, Delia ^c   Spadaccini, Roberta ^c,d  

^a UNIVERSITY OF VERONA   (Italy)

^b INSTITUTO DE QUÍMICA FÍSICA ROCASOLANO   (Spain)

^c UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^d UNIVERSITY OF SANNIO   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID PROTEIN; ANTINEOPLASTIC AGENT; BOVINE SEMINAL RIBONUCLEASE; DIMER; DOUBLE STRANDED RNA; MUTANT PROTEIN; NATURAL PRODUCT; OLIGOMER; POLYPEPTIDE; PROTEIN VARIANT; RIBONUCLEASE; RIBONUCLEASE A; RIBONUCLEASE A DERIVATIVE; SCAFFOLD PROTEIN; SINGLE STRANDED RNA; UNCLASSIFIED DRUG;

ALPHA HELIX; AMINO TERMINAL SEQUENCE; ANTINEOPLASTIC ACTIVITY; CARBOXY TERMINAL SEQUENCE; CHEMICAL MODIFICATION; COVALENT BOND; DRUG CYTOTOXICITY; DRUG DESIGN; DRUG STRUCTURE; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME CONFORMATION; ENZYME INACTIVATION; ENZYME STABILITY; ENZYME STRUCTURE; HUMAN; NONHUMAN; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN DOMAIN; PROTEIN LOCALIZATION; PROTEIN QUATERNARY STRUCTURE; PROTEIN RNA BINDING; REVIEW; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

3D-DOMAIN SWAPPING; ANTITUMOR RNASE; BOVINE SEMINAL RIBONUCLEASE; DIMERIC RNASE; PROTEIN AGGREGATION; RIBONUCLEASE A;

ANIMALS; ANTINEOPLASTIC AGENTS; CATALYTIC DOMAIN; DRUG DESIGN; ENDORIBONUCLEASES; HUMANS; MODELS, MOLECULAR; PROTEIN STRUCTURE, QUATERNARY; RIBONUCLEASE, PANCREATIC; STRUCTURE-ACTIVITY RELATIONSHIP;

BOVINAE;

EID: 84887410033     PISSN: 00145793     EISSN: 18733468     Source Type: Journal    
DOI: 10.1016/j.febslet.2013.09.038     Document Type: Review

References (100)

1. G.R. Marshall, J.A. Feng, and D.J. Kuster Back to the future: ribonuclease A Biopolymers 90 2008 259 277
2. A.M. Crestfield, W.H. Stein, and S. Moore On the aggregation of bovine pancreatic ribonuclease Arch. Biochem. Biophys. 1 1962 217 222
3. L. Mazzarella, S. Capasso, D. Demasi, G. Di Lorenzo, C.A. Mattia, and A. Zagari Bovine seminal ribonuclease: structure at 1.9 A resolution Acta Crystallogr. D Biol. Crystallogr. 49 1993 389 402
4. M.J. Bennett, S. Choe, and D. Eisenberg Domain swapping: entangling alliances between proteins Proc. Natl. Acad. Sci. USA 91 1994 3127 3131
5. Y. Liu, P.J. Hart, M.P. Schlunegger, and D. Eisenberg The crystal structure of a 3D domain-swapped dimer of RNase A at a 2.1-A resolution Proc. Natl. Acad. Sci. USA 95 1998 3437 3442
6. Y. Liu, G. Gotte, M. Libonati, and D. Eisenberg A domain-swapped RNase A dimer with implications for amyloid formation Nat. Struct. Biol. 8 2001 211 214
7. Y. Liu, G. Gotte, M. Libonati, and D. Eisenberg Structures of the two 3D domain-swapped RNase A trimers Protein Sci. 11 2002 371 380
8. M.P. Schlunegger, M.J. Bennett, and D. Eisenberg Oligomer formation by 3D domain swapping: a model for protein assembly and misassembly Adv. Protein Chem. 50 1997 61 122
9. K. Shameer, P.N. Shingate, S.C. Manjunath, M. Karthika, G. Pugalenthi, and R. Sowdhamini 3DSwap: Curated Knowledgebase of Proteins Involved in 3D Domain Swapping 2011 Database Oxford bar042
10. E.F. Fang, and T.B. Ng Ribonucleases of different origins with a wide spectrum of medicinal applications Biochim. Biophys. Acta 1815 2011 65 74
11. W. Ardelt, B. Ardelt, and Z. Darzynkiewicz Ribonucleases as potential modalities in anticancer therapy Eur. J. Pharmacol. 625 2009 181 189
12. R.F. Turcotte, L.D. Lavis, and R.T. Raines Onconase cytotoxicity relies on the distribution of its positive charge FEBS J. 276 2009 3846 3857
13. G. D'Errico, C. Ercole, M. Lista, E. Pizzo, A. Falanga, S. Galdiero, R. Spadaccini, and D. Picone Enforcing the positive charge of N-termini enhances membrane interaction and antitumor activity of bovine seminal ribonuclease Biochim. Biophys. Acta 1808 2011 3007 3015
14. J. Castro, M. Ribo, A. Benito, and M. Vilanova Mini-review: nucleus-targeted ribonucleases as antitumor drugs Curr. Med. Chem. 20 2013 1225 1231
15. B. Kobe, and J. Deisenhofer Crystal structure of porcine ribonuclease inhibitor, a protein with leucine-rich repeats Nature 366 1993 751 756
16. B. Kobe, and J. Deisenhofer Mechanism of ribonuclease inhibition by ribonuclease inhibitor protein based on the crystal structure of its complex with ribonuclease A J. Mol. Biol. 264 1996 1028 1043
17. R.J. Johnson, J.G. McCoy, C.A. Bingman, G.N. Phillips Jr., and R.T. Raines Inhibition of human pancreatic ribonuclease by the human ribonuclease inhibitor protein J. Mol. Biol. 368 2007 434 449
18. P.A. Leland, K.E. Staniszewski, B.M. Kim, and R.T. Raines Endowing human pancreatic ribonuclease with toxicity for cancer cells J. Biol. Chem. 276 2001 43095 43102
19. T.J. Rutkoski, E.L. Kurten, J.C. Mitchell, and R.T. Raines Disruption of shape-complementarity markers to create cytotoxic variants of ribonuclease A J. Mol. Biol. 354 2005 41 54
20. S.M. Fuchs, T.J. Rutkoski, V.M. Kung, R.T. Groeschl, and R.T. Raines Increasing the potency of a cytotoxin with an arginine graft Protein Eng. Des. Sel. 20 2007 505 509
21. T.J. Rutkoski, J.A. Kink, L.E. Strong, and R.T. Raines Site-specific PEGylation endows a mammalian ribonuclease with antitumor activity Cancer Biol. Ther. 12 2011 208 214
22. A. Di Donato, V. Cafaro, and G. D'Alessio Ribonuclease A can be transformed into a dimeric ribonuclease with antitumor activity J. Biol. Chem. 269 1994 17394 17396
23. C. Ercole, R.A. Colamarino, E. Pizzo, F. Fogolari, R. Spadaccini, and D. Picone Comparison of the structural and functional properties of RNase A and BS-RNase: a stepwise mutagenesis approach Biopolymers 91 2009 1009 1017
24. R. Piccoli, S. Vescia, S.H. Bridges, and G. D'Alessio The antitumor action of seminal ribonuclease tested with the plasmacytoma spleen colonization assay Ital. J. Biochem. 39 1990 242 249
25. R. Spadaccini, C. Ercole, M.A. Gentile, D. Sanfelice, R. Boelens, R. Wechselberger, G. Batta, A. Bernini, N. Niccolai, and D. Picone NMR studies on structure and dynamics of the monomeric derivative of BS-RNase: new insights for 3D domain swapping PLoS ONE 7 2012 e29076
26. R. Piccoli, M. Tamburrini, G. Piccialli, A. Di Donato, A. Parente, and G. D'Alessio The dual-mode quaternary structure of seminal RNase Proc. Natl. Acad. Sci. USA 89 1992 1870 1874
27. V. Cafaro, C. De Lorenzo, R. Piccoli, A. Bracale, M.R. Mastronicola, A. Di Donato, and G. D'Alessio The antitumor action of seminal ribonuclease and its quaternary conformations FEBS Lett. 359 1995 31 34
28. F. Sica, A. Di Fiore, A. Merlino, and L. Mazzarella 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 2004 36753 36760
29. A. Merlino, G. Avella, S. Di Gaetano, A. Arciello, R. Piccoli, L. Mazzarella, and F. Sica Structural features for the mechanism of antitumor action of a dimeric human pancreatic ribonuclease variant Protein Sci. 18 2009 50 57
30. J. Matousek, G. Gotte, P. Pouckova, J. Soucek, T. Slavik, F. Vottariello, and M. Libonati Antitumor activity and other biological actions of oligomers of ribonuclease A J. Biol. Chem. 278 2003 23817 23822
31. M. Naddeo, L. Vitagliano, A. Russo, G. Gotte, G. D'Alessio, and S. Sorrentino Interactions of the cytotoxic RNase A dimers with the cytosolic ribonuclease inhibitor FEBS Lett. 579 2005 2663 2668
32. A. Merlino, I. Russo Krauss, M. Perillo, C.A. Mattia, C. Ercole, D. Picone, A. Vergara, and F. Sica Toward an antitumor form of bovine pancreatic ribonuclease: the crystal structure of three non-covalent dimeric mutants Biopolymers 91 2009 1029 1037
33. A. Merlino, C. Ercole, D. Picone, E. Pizzo, L. Mazzarella, and F. Sica The buried diversity of bovine seminal ribonuclease: shape and cytotoxicity of the swapped non-covalent form of the enzyme J. Mol. Biol. 376 2008 427 437
34. M. Libonati, G. Gotte, and F. Vottariello A novel biological actions acquired by ribonuclease through oligomerization Curr. Pharm. Biotechnol. 9 2008 200 209
35. Y. Liu, and D. Eisenberg 3D domain swapping: as domains continue to swap Protein Sci. 11 2002 1285 1299
36. G. Gotte, F. Vottariello, and M. Libonati Thermal aggregation of ribonuclease A. A contribution to the understanding of the role of 3D domain swapping in protein aggregation J. Biol. Chem. 278 2003 10763 10769
37. M. Libonati, and G. Gotte Oligomerization of bovine ribonuclease A: structural and functional features of its multimers Biochem. J. 380 2004 311 327
38. G. Gotte, A. Mahmoud Helmy, C. Ercole, R. Spadaccini, D.V. Laurents, M. Donadelli, and D. Picone Double domain swapping in bovine seminal RNase: formation of distinct N- and C-swapped tetramers and multimers with increasing biological activities PLoS ONE 7 2012 e46804
39. L.M. Koharudin, L. Liu, and A.M. Gronenborn Different 3D domain-swapped oligomeric cyanovirin-N structures suggest trapped folding intermediates Proc. Natl. Acad. Sci. USA 110 2013 7702 7707
40. A.M. Gronenborn Protein acrobatics in pairs - dimerization via domain swapping Curr. Opin. Struct. Biol. 19 2009 39 49
41. M. Libonati, M. Bertoldi, and S. Sorrentino The activity on double-stranded RNA of aggregates of ribonuclease A higher than dimers increases as a function of the size of the aggregates Biochem. J. 318 Pt 1 1996 287 290
42. R.G. Fruchter, and A.M. Crestfield On the structure of ribonuclease dimer. Isolation and identification of monomers derived from inactive carboxymethyl dimers J. Biol. Chem. 240 1965 3875 3882
43. M.J. Bennett, M.P. Schlunegger, and D. Eisenberg 3D domain swapping: a mechanism for oligomer assembly Protein Sci. 4 1995 2455 2468
44. A. Nenci, G. Gotte, B. Maras, and M. Libonati Different susceptibility of the two dimers of ribonuclease A to subtilisin. Implications for their structure Biochim. Biophys. Acta 1545 2001 255 262
45. A. Merlino, L. Vitagliano, M.A. Ceruso, and L. Mazzarella Dynamic properties of the N-terminal swapped dimer of ribonuclease A Biophys. J. 86 2004 2383 2391
46. A. Merlino, M.A. Ceruso, L. Vitagliano, and L. Mazzarella Open interface and large quaternary structure movements in 3D domain swapped proteins: insights from molecular dynamics simulations of the C-terminal swapped dimer of ribonuclease A Biophys. J. 88 2005 2003 2012
47. G. Gotte, and M. Libonati Two different forms of aggregated dimers of ribonuclease A Biochim. Biophys. Acta 1386 1998 106 112
48. G. Gotte, M. Bertoldi, and M. Libonati Structural versatility of bovine ribonuclease A. Distinct conformers of trimeric and tetrameric aggregates of the enzyme Eur. J. Biochem. 265 1999 680 687
49. Y.B. Yan, J. Zhang, H.W. He, and H.M. Zhou Oligomerization and aggregation of bovine pancreatic ribonuclease A: characteristic events observed by FTIR spectroscopy Biophys. J. 90 2006 2525 2533
50. R. Geiger, M. Gautschi, F. Thor, A. Hayer, and A. Helenius Folding, quality control, and secretion of pancreatic ribonuclease in live cells J. Biol. Chem. 286 2011 5813 5822
51. G. Gotte, M. Donadelli, D.V. Laurents, F. Vottariello, M. Morbio, and M. Libonati Increase of RNase a N-terminus polarity or C-terminus apolarity changes the two domains' propensity to swap and form the two dimeric conformers of the protein Biochemistry 45 2006 10795 10806
52. S. Sorrentino, R. Barone, E. Bucci, G. Gotte, N. Russo, M. Libonati, and G. D'Alessio The two dimeric forms of RNase A FEBS Lett. 466 2000 35 39
53. A. Nenci, G. Gotte, M. Bertoldi, and M. Libonati Structural properties of trimers and tetramers of ribonuclease A Protein Sci. 10 2001 2017 2027
54. A. Benito, D.V. Laurents, M. Ribo, and M. Vilanova The structural determinants that lead to the formation of particular oligomeric structures in the pancreatic-type ribonuclease family Curr. Protein Pept. Sci. 9 2008 370 393
55. G. Gotte, and M. Libonati Oligomerization of ribonuclease A: two novel three-dimensional domain-swapped tetramers J. Biol. Chem. 279 2004 36670 36679
56. G. Gotte, and M. Libonati Oligomerization of ribonuclease A under reducing conditions Biochim. Biophys. Acta 1784 2008 638 650
57. G. Gotte, D.V. Laurents, and M. Libonati Three-dimensional domain-swapped oligomers of ribonuclease A: identification of a fifth tetramer, pentamers and hexamers, and detection of trace heptameric, octameric and non-americ species Biochim. Biophys. Acta 1764 2006 44 54
58. G. Cozza, S. Moro, and G. Gotte Elucidation of the ribonuclease a aggregation process mediated by 3D domain swapping: A computational approach reveals possible new multimeric structures Biopolymers 89 2008 26 39
59. F. Vottariello, E. Giacomelli, R. Frasson, N. Pozzi, V. De Filippis, and G. Gotte RNase A oligomerization through 3D domain swapping is favoured by a residue located far from the swapping domains Biochimie 93 2011 1846 1857
60. M.R. Sawaya, S. Sambashivan, R. Nelson, M.I. Ivanova, S.A. Sievers, M.I. Apostol, M.J. Thompson, M. Balbirnie, J.J. Wiltzius, H.T. McFarlane, A.O. Madsen, C. Riekel, and D. Eisenberg Atomic structures of amyloid cross-beta spines reveal varied steric zippers Nature 447 2007 453 457
61. G. Gotte, M. Libonati, and D.V. Laurents Glycosylation and specific deamidation of ribonuclease B affect the formation of three-dimensional domain-swapped oligomers J. Biol. Chem. 278 2003 46241 46251
62. J.P. Lopez-Alonso, M. Bruix, J. Font, M. Ribo, M. Vilanova, M. Rico, G. Gotte, M. Libonati, C. Gonzalez, and D.V. Laurents Formation, structure, and dissociation of the ribonuclease S three-dimensional domain-swapped dimer J. Biol. Chem. 281 2006 9400 9406
63. F.M. Richards, and P.J. Vithayathil The preparation of subtilisn-modified ribonuclease and the separation of the peptide and protein components J. Biol. Chem. 234 1959 1459 1465
64. G. D'Alessio, A. Parente, C. Guida, and E. Leone Dimeric structure of seminal ribonuclease FEBS Lett. 27 1972 285 288
65. R.G. Fruchter, and A.M. Crestfield Preparation and properties of two active forms of ribonuclease dimer J. Biol. Chem. 240 1965 3868 3874
66. C. Park, and R.T. Raines Dimer formation by a "monomeric" protein Protein Sci. 9 2000 2026 2033
67. A. Marzotto, and L. Galzigna Molecular aggregation of bovine pancreatic ribonuclease induced by substrate Arch. Biochem. Biophys. 137 1970 373 378
68. P.K. Teng, N.J. Anderson, L. Goldschmidt, M.R. Sawaya, S. Sambashivan, and D. Eisenberg Ribonuclease A suggests how proteins self-chaperone against amyloid fiber formation Protein Sci. 21 2012 26 37
69. L. Goldschmidt, P.K. Teng, R. Riek, and D. Eisenberg Identifying the amylome, proteins capable of forming amyloid-like fibrils Proc. Natl. Acad. Sci. USA 107 2010 3487 3492
70. M. Torrent, F. Odorizzi, M.V. Nogues, and E. Boix Eosinophil cationic protein aggregation: identification of an N-terminus amyloid prone region Biomacromolecules 11 2010 1983 1990
71. S. Sambashivan, Y. Liu, M.R. Sawaya, M. Gingery, and D. Eisenberg Amyloid-like fibrils of ribonuclease A with three-dimensional domain-swapped and native-like structure Nature 437 2005 266 269
72. M.J. Bennett, M.R. Sawaya, and D. Eisenberg Deposition diseases and 3D domain swapping Structure 14 2006 811 824
73. J.P. Lopez-Alonso, G. Gotte, and D.V. Laurents Kinetic analysis provides insight into the mechanism of ribonuclease A oligomer formation Arch. Biochem. Biophys. 489 2009 41 47
74. F.G. Pearce, M.D. Griffin, and J.A. Gerrard Does domain swapping improve the stability of RNase A? Biochem. Biophys. Res. Commun. 382 2009 114 118
75. E. Notomista, J.M. Mancheno, O. Crescenzi, A. Di Donato, J. Gavilanes, and G. D'Alessio The role of electrostatic interactions in the antitumor activity of dimeric RNases FEBS J. 273 2006 3687 3697
76. V. Cafaro, A. Bracale, A. Di Maro, S. Sorrentino, G. D'Alessio, and A. Di Donato New muteins of RNase A with enhanced antitumor action FEBS Lett. 437 1998 149 152
77. F. Leich, J. Koditz, R. Ulbrich-Hofman, and U. Arnold Tandemization endows bovine pancreatic ribonuclease with cytotoxic activity J. Mol. Biol. 358 2006 1305 1313
78. U. Arnold, F. Leich, P. Neumann, H. Lilie, and R. Ulbrich-Hofmann Crystal structure of RNase A tandem enzymes and their interaction with the cytosolic ribonuclease inhibitor FEBS J. 278 2011 331 340
79. J.P. Lopez-Alonso, M. Bruix, J. Font, M. Ribo, M. Vilanova, M.A. Jimenez, J. Santoro, C. Gonzalez, and D.V. Laurents NMR spectroscopy reveals that RNase A is chiefly denatured in 40% acetic acid: implications for oligomer formation by 3D domain swapping J. Am. Chem. Soc. 132 2010 1621 1630
80. K.H. Miller, J.R. Karr, and S. Marqusee A hinge region cis-proline in ribonuclease A acts as a conformational gatekeeper for C-terminal domain swapping J. Mol. Biol. 400 2010 567 578
81. A. Merlino, D. Picone, C. Ercole, A. Balsamo, and F. Sica Chain termini cross-talk in the swapping process of bovine pancreatic ribonuclease Biochimie 94 2012 1108 1118
82. C. Ercole, J.P. Lopez-Alonso, J. Font, M. Ribo, M. Vilanova, D. Picone, and D.V. Laurents Crowding agents and osmolytes provide insight into the formation and dissociation of RNase A oligomers Arch. Biochem. Biophys. 506 2011 123 129
83. E. Bucci, L. Vitagliano, R. Barone, S. Sorrentino, G. D'Alessio, and G. Graziano On the thermal stability of the two dimeric forms of ribonuclease A Biophys. Chem. 116 2005 89 95
84. J.S. Kim, J. Soucek, J. Matousek, and R.T. Raines Mechanism of ribonuclease cytotoxicity J. Biol. Chem. 270 1995 31097 31102
85. A. Canals, J. Pous, A. Guasch, A. Benito, M. Ribo, M. Vilanova, and M. Coll The structure of an engineered domain-swapped ribonuclease dimer and its implications for the evolution of proteins toward oligomerization Structure 9 2001 967 976
86. C. Ercole, R. Spadaccini, C. Alfano, T. Tancredi, and D. Picone A new mutant of bovine seminal ribonuclease with a reversed swapping propensity Biochemistry 46 2007 2227 2232
87. C. Giancola, C. Ercole, I. Fotticchia, R. Spadaccini, E. Pizzo, G. D'Alessio, and D. Picone Structure-cytotoxicity relationships in bovine seminal ribonuclease: new insights from heat and chemical denaturation studies on variants FEBS J. 278 2011 111 122
88. D. Wang, G. Wilson, and S. Moore Preparation of cross-linked dimers of pancreatic ribonuclease Biochemistry 15 1976 660 665
89. G. Gotte, L. Testolin, C. Costanzo, S. Sorrentino, U. Armato, and M. Libonati Cross-linked trimers of bovine ribonuclease A: activity on double-stranded RNA and antitumor action FEBS Lett. 415 1997 308 312
90. B.L. Simons, H. Kaplan, S.M. Fournier, T. Cyr, and M.A. Hefford A novel cross-linked RNase A dimer with enhanced enzymatic properties Proteins 66 2007 183 195
91. F. Vottariello, C. Costanzo, G. Gotte, and M. Libonati "Zero-length" dimers of ribonuclease A: further characterization and no evidence of cytotoxicity Bioconjug. Chem. 21 2010 635 645
92. P. Pouckova, M. Morbio, F. Vottariello, D.V. Laurents, J. Matousek, J. Soucek, G. Gotte, M. Donadelli, C. Costanzo, and M. Libonati Cytotoxicity of polyspermine-ribonuclease A and polyspermine-dimeric ribonuclease A Bioconjug. Chem. 18 2007 1946 1955
93. R. Piccoli, S. Di Gaetano, C. De Lorenzo, M. Grauso, C. Monaco, D. Spalletti-Cernia, P. Laccetti, J. Cinatl, J. Matousek, and G. D'Alessio A dimeric mutant of human pancreatic ribonuclease with selective cytotoxicity toward malignant cells Proc. Natl. Acad. Sci. USA 96 1999 7768 7773
94. S. Di Gaetano, G. D'Alessio, and R. Piccoli Second generation antitumour human RNase: significance of its structural and functional features for the mechanism of antitumour action Biochem. J. 358 2001 241 247
95. R. Berisio, F. Sica, C. De Lorenzo, A. Di Fiore, R. Piccoli, A. Zagari, and L. Mazzarella Crystal structure of the dimeric unswapped form of bovine seminal ribonuclease FEBS Lett. 554 2003 105 110
96. P.A. Leland, and R.T. Raines Cancer chemotherapy-ribonucleases to the rescue Chem. Biol. 8 2001 405 413
97. A.A. Makarov, and O.N. Ilinskaya Cytotoxic ribonucleases: molecular weapons and their targets FEBS Lett. 540 2003 15 20
98. U. Arnold, and R. Ulbrich-Hofmann Natural and engineered ribonucleases as potential cancer therapeutics Biotechnol. Lett. 28 2006 1615 1622
99. T.J. Rutkoski, and R.T. Raines Evasion of ribonuclease inhibitor as a determinant of ribonuclease cytotoxicity Curr. Pharm. Biotechnol. 9 2008 185 189
100. E. Boix, Y. Wu, V.M. Vasandani, S.K. Saxena, W. Ardelt, J. Ladner, and R.J. Youle Role of the N terminus in RNase A homologues: differences in catalytic activity, ribonuclease inhibitor interaction and cytotoxicity J. Mol. Biol. 257 1996 992 1007