3fd7

Crystal structure of Onconase C87A/C104A-ONC

spinqualitylabelsall models 3fd7, resolution 1.53Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3fd7 is a 2 chain structure with sequence from Litpi. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, GOL, SO4 NonStd Res: PCA Related: 2kb6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [RNP30_RANPI] Basic protein with antiproliferative/cytotoxic activity against several tumor cell lines in vitro, as well as antitumor in vivo. It exhibits a ribonuclease-like activity against high molecular weight ribosomal RNA. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The two homologous proteins ribonuclease A and onconase fold through conserved initial contacts but differ significantly in their thermodynamic stability. A disulfide bond is located in the folding initiation site of onconase (the C-terminal part of the protein molecule) that is missing in ribonuclease A, whereas the other three disulfide bonds of onconase are conserved in ribonuclease A. Consequently, the deletion of this C-terminal disulfide bond (C87-C104) allows the impact of the contacts in this region on the folding of onconase to be studied. We found the C87A/C104A-onconase variant to be less active and less stable than the wild-type protein, whereas the tertiary structure, which was determined by both X-ray crystallography and NMR spectroscopy, was only marginally affected. The folding kinetics of the variant, however, were found to be changed considerably in comparison to wild-type onconase. Proton exchange experiments in combination with two-dimensional NMR spectroscopy revealed differences in the native-state dynamics of the two proteins in the folding initiation site, which are held responsible for the changed folding mechanism. Likewise, the molecular dynamics simulation of the unfolding reaction indicated disparities for both proteins. Our results show that the high stability of onconase is based on the efficient stabilization of the folding initiation site by the C-terminal disulfide bond. The formation of the on-pathway intermediate, which is detectable during the folding of the wild-type protein and promotes the fast and efficient refolding reaction, requires the presence of this covalent bond. Impact of the C-terminal disulfide bond on the folding and stability of onconase.,Schulenburg C, Weininger U, Neumann P, Meiselbach H, Stubbs MT, Sticht H, Balbach J, Ulbrich-Hofmann R, Arnold U Chembiochem. 2010 May 3;11(7):978-86. PMID:20349493 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA