|
|
| (3 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==The Solution NMR Structure and Dynamics of a Recombinant Onconase with Altered N-terminal and Met23 residues== | | ==The Solution NMR Structure and Dynamics of a Recombinant Onconase with Altered N-terminal and Met23 residues== |
| - | <StructureSection load='1pu3' size='340' side='right' caption='[[1pu3]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1pu3' size='340' side='right'caption='[[1pu3]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1pu3]] 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=1PU3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1PU3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1pu3]] 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=1PU3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PU3 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1onc|1onc]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 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=1pu3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pu3 OCA], [http://pdbe.org/1pu3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1pu3 RCSB], [http://www.ebi.ac.uk/pdbsum/1pu3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1pu3 ProSAT]</span></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=1pu3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pu3 OCA], [https://pdbe.org/1pu3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pu3 RCSB], [https://www.ebi.ac.uk/pdbsum/1pu3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pu3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. | + | [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]] |
| Line 14: |
Line 14: |
| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pu/1pu3_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pu/1pu3_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> |
| Line 32: |
Line 32: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Litpi]] | + | [[Category: Large Structures]] |
| - | [[Category: Chang, C F]] | + | [[Category: Lithobates pipiens]] |
| - | [[Category: Gorbatyuk, V Y]] | + | [[Category: Chang CF]] |
| - | [[Category: Huang, T H]] | + | [[Category: Gorbatyuk VY]] |
| - | [[Category: Tsai, C K]] | + | [[Category: Huang TH]] |
| - | [[Category: Bowl-shaped folding of the two sheet]] | + | [[Category: Tsai CK]] |
| - | [[Category: Hydrolase]]
| + | |
| 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
Onconase (rONC), otherwise known as ranpirnase or P-30 protein, which was initially purified from extracts of Rana pipiens oocytes and early embryos, exhibits anticancer activity both in vitro and in vivo and is in phase III clinical trials for tumor therapy. We have determined the solution NMR structure of a recombinant onconase with Met(-1), Gln1, and Leu23 residues (M-1, Q1, M23L)rONC. The 20 best solution structures had a backbone root mean square deviation of 0.41 +/- 0.09 A with respect to the average structure. The energy-minimized average NMR structure had a backbone root mean square deviation of 0.72 A from the x-ray crystallographic structure of native onconase; however, the orientation of the N-terminal residue in the two structures was very different. Comparison of the 15N HSQC spectrum of (M-1, Q1, M23L)rONC with that of a mutant E1S-rONC, which is identical to the nONC except with the N-terminal pyroglutamyl residue replaced by Ser, showed that N-terminal and residue 23 mutations induced structural changes in regions beyond the mutation sites. Model-free analysis of the backbone amide 15N-T1, 15N-T2, and 15N-1H NOE relaxation data for (M-1, Q1, M23L)rONC and E1S-rONC revealed that the E1S-rONC molecule showed very little flexibility, whereas (M-1, Q1, M23L)rONC exhibited substantial flexibility, which may account for the previously observed reduced stability and increased protease susceptibility. The alpha1 helix and beta-sheets of (M-1, Q1, M23L)rONC displayed bending motions. These data provided strong evidence for the presence of an N-terminal hydrogen bond network in E1S-rONC, but not in (M-1, Q1, M23L)rONC.
Effect of N-terminal and Met23 mutations on the structure and dynamics of onconase.,Gorbatyuk VY, Tsai CK, Chang CF, Huang TH J Biol Chem. 2004 Feb 13;279(7):5772-80. Epub 2003 Nov 26. PMID:14645226[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gorbatyuk VY, Tsai CK, Chang CF, Huang TH. Effect of N-terminal and Met23 mutations on the structure and dynamics of onconase. J Biol Chem. 2004 Feb 13;279(7):5772-80. Epub 2003 Nov 26. PMID:14645226 doi:10.1074/jbc.M311233200
|
