A novel biological actions acquired by ribonuclease through oligomerization.
After a short introduction with some examples of cytotoxic ribonucleases, the importance of natural or artificial dimerization (oligomerization) as a way for a ribonuclease to acquire novel functional properties has been pointed out. In particular, the role of the three dimensional domain swapping mechanism in bovine pancreatic ribonuclease A oligomerization, as well as its impact for the acquisition of novel biological functions (among which a remarkable antitumor action) by the enzyme protein in oligomeric form have been discussed. Finally, the structural and functional features that could explain why oligomeric ribonuclease A becomes able to display a cytotoxic activity, and the possible use and limits of the three dimensional domain-swapped oligomers of ribonuclease A as anticancer therapeutic agents have been described and discussed.
Libonati
M
M
Dipartimento di Scienze Morfologico-Biomediche, Sezione di Chimica Biologica, Istituti Biologici, Strada Le Grazie 8, I-37134 Verona, Italy. massimo.libonati@univr.it
Gotte
G
G
Vottariello
F
F
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011487:Protein Conformation; D021381:Protein Transport; D012334:RNA, Neoplasm / Q000037:antagonists & inhibitors; D012260:Ribonucleases / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D012334:RNA, Neoplasm; D012260:Ribonucleases