Letter to the Editor: 1H and 15N sequential assignment and solution secondary structure of 15N labelled human pancreatic ribonuclease
| Autor: | El-Joubary, A., Bruix, M., Santoro, Jorge, Cafaro, V., Scognamiglio, R., Di Donato, A., D'Alessio, G., Kövér, Katalin E., Batta, Gy., Szilágyi, L., Rico, Manuel |
|---|---|
| Přispěvatelé: | European Commission, Ministerio de Asuntos Exteriores (España) |
| Rok vydání: | 1999 |
| Předmět: | |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | Several members of the RNase A (bovine pancreatic ribonuclease) superfamily exhibit anticancer activity. Among the mammalian members of the superfamily, most of the antitumour activity studies have been carried out with a dimeric RNase from bovine seminal vesicles (BS-RNase) (Youle and D’Alessio, 1997). These studies show that dimer formation is crucial for cytotoxicity. Investigations are underway to transfer by protein engineering the structural determinants responsible for the antitumour activity of BS-RNase to a human immunocompatible backbone (Piccoli et al., 1999). Knowledge of the 3D structures of the involved proteins is central to rationally fulfil this objective. As a first step, human pancreatic ribonuclease (HPRNase), a 127-residue monomeric protein (Beintema et al., 1984) was constructed (Russo et al., 1993). The expressed recombinant protein was undistinguishable from the natural product isolated from human pancreas (Weickmann et al., 1981). Here, we present the assignment of practically all of its 1H and 15N spectral resonances, as well as its secondary structure in aqueous solution. The cytotoxic activity of ribonucleases has been related to their ability to evade the cytosolic ribonuclease inhibitor (RI) (Murthy and Sirdeshmukh, 1992). The structure of HP-RNase will be useful to introduce changes in it in order to increase its resistance to RI. This work was supported by the European Commission under the INCO-Copernicus Project No. IC15 CT 96-0903. The assistance of the Ministerio de Asuntos Exteriores (Spain) and OMFB (Hungary) (project E26/97) is gratefully acknowledged. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|