1YV4: X-Ray Structure Of M23l Onconase At 100k

Onconase (ONC), a member of the RNase A superfamily extracted from oocytes of Rana pipiens, is an effective cancer killer. It is currently used in treatment of various forms of cancer. ONC antitumor properties depend on its ribonucleolytic activity that is low in comparison with other members of the superfamily. The most damaging side effect from Onconase treatment is renal toxicity, which seems to be caused by the unusual stability of the enzyme. Therefore, mutants with reduced thermal stability and/or increased catalytic activity may have significant implications for human cancer chemotherapy. In this context, we have determined the crystal structures of two Onconase mutants (M23L-ONC and C87S,des103-104-ONC) and performed molecular dynamic simulations of ONC and C87S,des103-104-ONC with the aim of explaining on structural grounds the modifications of the activity and thermal stability of the mutants. The results also provide the molecular bases to explain the lower catalytic activity of Onconase compared with RNase A and the unusually high thermal stability of the amphibian enzyme.
PDB ID: 1YV4Download
MMDB ID: 32151
PDB Deposition Date: 2005/2/15
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 1.51  Å
Source Organism:
Similar Structures:
Biological Unit for 1YV4: monomeric; determined by author
Molecular Components in 1YV4
Label Count Molecule
Protein (1 molecule)
P-30 Protein
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

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