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| | <StructureSection load='3f8g' size='340' side='right'caption='[[3f8g]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='3f8g' size='340' side='right'caption='[[3f8g]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3f8g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F8G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F8G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3f8g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F8G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F8G FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1bsr|1bsr]], [[1r3m|1r3m]], [[2k11|2k11]], [[1e21|1e21]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RNASE1, RIB1, RNS1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Pancreatic_ribonuclease Pancreatic ribonuclease], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.27.5 3.1.27.5] </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=3f8g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f8g OCA], [https://pdbe.org/3f8g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f8g RCSB], [https://www.ebi.ac.uk/pdbsum/3f8g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f8g 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=3f8g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f8g OCA], [https://pdbe.org/3f8g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f8g RCSB], [https://www.ebi.ac.uk/pdbsum/3f8g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f8g ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/RNAS1_HUMAN RNAS1_HUMAN]] Endonuclease that catalyzes the cleavage of RNA on the 3' side of pyrimidine nucleotides. Acts on single stranded and double stranded RNA.<ref>PMID:17350650</ref>
| + | [https://www.uniprot.org/uniprot/RNAS1_HUMAN RNAS1_HUMAN] Endonuclease that catalyzes the cleavage of RNA on the 3' side of pyrimidine nucleotides. Acts on single stranded and double stranded RNA.<ref>PMID:17350650</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pancreatic ribonuclease]]
| + | [[Category: Avella G]] |
| - | [[Category: Avella, G]] | + | [[Category: Mazzarella L]] |
| - | [[Category: Mazzarella, L]] | + | [[Category: Merlino A]] |
| - | [[Category: Merlino, A]] | + | [[Category: Sica F]] |
| - | [[Category: Sica, F]] | + | |
| - | [[Category: 3d domain swapping]]
| + | |
| - | [[Category: Antitumor agent]]
| + | |
| - | [[Category: Dimer]]
| + | |
| - | [[Category: Endonuclease]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Nuclease]]
| + | |
| - | [[Category: Ribonuclease]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Unswapped dimer]]
| + | |
| Structural highlights
Function
RNAS1_HUMAN Endonuclease that catalyzes the cleavage of RNA on the 3' side of pyrimidine nucleotides. Acts on single stranded and double stranded RNA.[1]
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
A specialized class of RNases shows a high cytotoxicity toward tumor cell lines, which is critically dependent on their ability to reach the cytosol and to evade the action of the ribonuclease inhibitor (RI). The cytotoxicity and antitumor activity of bovine seminal ribonuclease (BSRNase), which exists in the native state as an equilibrium mixture of a swapped and an unswapped dimer, are peculiar properties of the swapped form. A dimeric variant (HHP2-RNase) of human pancreatic RNase, in which the enzyme has been engineered to reproduce the sequence of BSRNase helix-II (Gln28-->Leu, Arg31-->Cys, Arg32-->Cys, and Asn34-->Lys) and to eliminate a negative charge on the surface (Glu111-->Gly), is also extremely cytotoxic. Surprisingly, this activity is associated also to the unswapped form of the protein. The crystal structure reveals that on this molecule the hinge regions, which are highly disordered in the unswapped form of BSRNase, adopt a very well-defined conformation in both subunits. The results suggest that the two hinge peptides and the two Leu28 side chains may provide an anchorage to a transient noncovalent dimer, which maintains Cys31 and Cys32 of the two subunits in proximity, thus stabilizing a quaternary structure, similar to that found for the noncovalent swapped dimer of BSRNase, that allows the molecule to escape RI and/or to enhance the formation of the interchain disulfides.
Structural features for the mechanism of antitumor action of a dimeric human pancreatic ribonuclease variant.,Merlino A, Avella G, Di Gaetano S, Arciello A, Piccoli R, Mazzarella L, Sica F Protein Sci. 2009 Jan;18(1):50-7. PMID:19177350[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Johnson RJ, McCoy JG, Bingman CA, Phillips GN Jr, Raines RT. Inhibition of human pancreatic ribonuclease by the human ribonuclease inhibitor protein. J Mol Biol. 2007 Apr 27;368(2):434-49. Epub 2007 Feb 9. PMID:17350650 doi:10.1016/j.jmb.2007.02.005
- ↑ Merlino A, Avella G, Di Gaetano S, Arciello A, Piccoli R, Mazzarella L, Sica F. Structural features for the mechanism of antitumor action of a dimeric human pancreatic ribonuclease variant. Protein Sci. 2009 Jan;18(1):50-7. PMID:19177350 doi:10.1002/pro.6
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