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| | ==Solution structure of onconase C87A/C104A== | | ==Solution structure of onconase C87A/C104A== |
| - | <StructureSection load='2kb6' size='340' side='right' caption='[[2kb6]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2kb6' size='340' side='right'caption='[[2kb6]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kb6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Litpi Litpi]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KB6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KB6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kb6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lithobates_pipiens Lithobates pipiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KB6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KB6 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 10 models</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2kb6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kb6 OCA], [http://pdbe.org/2kb6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kb6 RCSB], [http://www.ebi.ac.uk/pdbsum/2kb6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2kb6 ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2kb6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kb6 OCA], [https://pdbe.org/2kb6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kb6 RCSB], [https://www.ebi.ac.uk/pdbsum/2kb6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kb6 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RNP30_RANPI 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. | + | [https://www.uniprot.org/uniprot/RNP30_LITPI RNP30_LITPI] 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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kb/2kb6_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kb/2kb6_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Litpi]] | + | [[Category: Large Structures]] |
| - | [[Category: Arnold, U]] | + | [[Category: Lithobates pipiens]] |
| - | [[Category: Balbach, J]] | + | [[Category: Arnold U]] |
| - | [[Category: Schulenburg, C]] | + | [[Category: Balbach J]] |
| - | [[Category: Ulbrich-Hofmann, R]] | + | [[Category: Schulenburg C]] |
| - | [[Category: Weininger, U]] | + | [[Category: Ulbrich-Hofmann R]] |
| - | [[Category: Endonuclease]]
| + | [[Category: Weininger U]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Nuclease]]
| + | |
| - | [[Category: Protein]]
| + | |
| - | [[Category: Pyrrolidone carboxylic acid]]
| + | |
| - | [[Category: Rnase]]
| + | |
| Structural highlights
Function
RNP30_LITPI 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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Schulenburg C, Weininger U, Neumann P, Meiselbach H, Stubbs MT, Sticht H, Balbach J, Ulbrich-Hofmann R, Arnold U. Impact of the C-terminal disulfide bond on the folding and stability of onconase. Chembiochem. 2010 May 3;11(7):978-86. PMID:20349493 doi:10.1002/cbic.200900773
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