HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

X-ray structure of two crystalline forms of a streptomycete ribonuclease with cytotoxic activity.

Abstract
Ribonuclease (RNase) Sa3 is secreted by the Gram-positive bacterium Streptomyces aureofaciens. The enzyme catalyzes the cleavage of RNA on the 3' side of guanosine residues. Here, x-ray diffraction analysis was used to determine the three-dimensional structure of two distinct crystalline forms of RNase Sa3 to a resolution of 2.0 and 1.7 A. These two structures are similar to each other as well as to that of a homolog, RNase Sa. All of the key active-site residues of RNase Sa (Asn(42), Glu(44), Glu(57), Arg(72), and His(88)) are located in the putative active site of RNase Sa3. Also herein, RNase Sa3 is shown to be toxic to human erythroleukemia cells in culture. Like onconase, which is an amphibian ribonuclease in Phase III clinical trials as a cancer chemotherapeutic, RNase Sa3 is not inhibited by the cytosolic ribonuclease inhibitor protein. Thus, a prokaryotic ribonuclease can be toxic to mammalian cells.
AuthorsJozef Sevcik, Lubica Urbanikova, Peter A Leland, Ronald T Raines
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 277 Issue 49 Pg. 47325-30 (Dec 6 2002) ISSN: 0021-9258 [Print] United States
PMID12228255 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Isoenzymes
  • Glutamine
  • Histidine
  • Asparagine
  • Arginine
  • Ribonucleases
  • ribonuclease Sa3
Topics
  • Amino Acid Sequence
  • Arginine (chemistry)
  • Asparagine (chemistry)
  • Binding Sites
  • Dose-Response Relationship, Drug
  • Glutamine (chemistry)
  • Histidine (chemistry)
  • Humans
  • Isoenzymes (chemistry)
  • K562 Cells
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Ribonucleases (antagonists & inhibitors, chemistry)
  • Sequence Homology, Amino Acid
  • Streptomyces aureofaciens (enzymology)
  • Temperature
  • Tumor Cells, Cultured
  • X-Ray Diffraction

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: