Contribution of structural peculiarities of onconase to its high stability and folding kinetics

Biochemistry
Ulrich ArnoldRenate Ulbrich-Hofmann

Abstract

Onconase (ONC) from Rana pipiens is the smallest member of the ribonuclease A (RNase A) superfamily. Despite a tertiary structure similar to RNase A, ONC is distinguished by an extremely high thermodynamic stability. In the present paper we have probed the significance of three structural regions, which exhibit structural peculiarities in comparison to RNase A, for the stability of ONC to temperature and guanidine hydrochloride induced denaturation: (i) the N-terminal pyroglutamate residue, (ii) the hydrophobic cluster between helix I and the first beta-sheet, and (iii) the C-terminal disulfide bond. For this purpose, the enzyme variants <E1E-, <E1P-, F28T-, F28A-, F36Y-, and C87A/C104A-ONC were produced and studied in equilibrium and kinetic measurements. The destabilizing influence of the mutations strongly depended on the modified structural region. The exchanges of the N-terminal pyroglutamate (<E1E- and <E1P-ONC) had the smallest impact (DeltaDeltaG([D])50% = 4.2 and 7.0 kJ mol(-)(1)), while interferences in the hydrophobic cluster (F28T-, F28A-, and F36Y-ONC) had larger effects (DeltaDeltaG([D])50% = 22.2, 20.9, and 19.5 kJ mol(-)(1)). The removal of the C-terminal disulfide bond (C87A/C104A-ONC) showed the largest influe...Continue Reading

References

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Citations

Jul 12, 2012·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Henrike WestekemperRalf A Hilger
Aug 12, 2006·Biotechnology Letters·Ulrich Arnold, Renate Ulbrich-Hofmann
Nov 4, 2008·Biological Chemistry·Gerard TorrentMaria Vilanova
Jan 25, 2008·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·J Eugene Lee, Ronald T Raines
Aug 16, 2011·Biophysical Chemistry·Salvador Casares-AtienzaMaria M Garcia-Mira
Oct 15, 2009·European Journal of Pharmacology·Wojciech ArdeltZbigniew Darzynkiewicz
Jan 22, 2009·Biophysical Chemistry·Pascal Pecher, Ulrich Arnold
Nov 16, 2007·Journal of Molecular Biology·J Eugene LeeRonald T Raines
Jun 16, 2009·The FEBS Journal·Rebecca F TurcotteRonald T Raines
Oct 20, 2007·The FEBS Journal·Cindy SchulenburgUlrich Arnold
May 19, 2012·The FEBS Journal·Ulrich Arnold, Michael Schöpfel
Dec 15, 2012·Protein Science : a Publication of the Protein Society·Ulrich ArnoldRonald T Raines
Mar 30, 2010·Chembiochem : a European Journal of Chemical Biology·Cindy SchulenburgUlrich Arnold
Jun 29, 2015·Biophysical Chemistry·Knut KölbelRenate Ulbrich-Hofmann
Jun 24, 2016·Organic & Biomolecular Chemistry·Ulrich Arnold, Ronald T Raines
Aug 7, 2009·Biochemistry·Cindy SchulenburgUlrich Arnold
Jun 13, 2009·Biochemistry·Dagmar SchlenzigHans-Ulrich Demuth

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