Back to Search
Start Over
Hints on the evolutionary design of a dimeric RNase withspecialbioactions
- Source :
- Scopus-Elsevier
- Publication Year :
- 1995
- Publisher :
- Wiley, 1995.
-
Abstract
- Residues P19, L28, C31, and C32 have been implicated (Di Donato A, Cafaro V, D'Alessio G, 1994, J Biol Chem 269:17394-17396; Mazzarella L, Vitagliano L, Zagari A, 1995, Proc Natl Acad Sci USA: forthcoming) with key roles in determining the dimeric structure and the N-terminal domain swapping of seminal RNase. In an attempt to have a clearer understanding of the structural and functional significance of these residues in seminal RNase, a series of mutants of pancreatic RNase A was constructed in which one or more of the four residues were introduced into RNase A. The RNase mutants were examined for: (1) the ability to form dimers; (2) the capacity to exchange their N-terminal domains; (3) resistance to selective cleavage by subtilisin; and (4) antitumor activity. The experiments demonstrated that: (1) the presence of intersubunit disulfides is both necessary and sufficient for engendering a stably dimeric RNase; (2) all four residues play a role in determining the exchange of N-terminal domains; (3) the exchange is the molecular basis for the RNase antitumor action; and (4) this exchange is not a prerequisite in an evolutionary mechanism for the generation of dimeric RNases.
- Subjects :
- Macromolecular Substances
RNase P
Mutant
Antineoplastic Agents
Biology
Biochemistry
RNase PH
seminal ribonuclease
Ribonucleases
evolution
Animals
Subtilisins
Ribonuclease
Pancreas
Molecular Biology
mutants
antitumor action
Mutagenesis
Subtilisin
Protein engineering
Biological Evolution
RNase MRP
Molecular Probes
Mutagenesis, Site-Directed
biology.protein
Research Article
Subjects
Details
- ISSN :
- 1469896X and 09618368
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- Protein Science
- Accession number :
- edsair.doi.dedup.....ce6e80cae69fb32d05989a2908c59635