1dza: Difference between revisions

New page: left|200px<br /> <applet load="1dza" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dza, resolution 1.65Å" /> '''3-D STRUCTURE OF A ...
 
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[[Image:1dza.gif|left|200px]]<br />
<applet load="1dza" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1dza, resolution 1.65&Aring;" />
'''3-D STRUCTURE OF A HP-RNASE'''<br />


==Overview==
==3-D structure of a HP-RNase==
We have determined the crystal structure of a human pancreatic, ribonuclease or RNase 1 variant at 1.65 A resolution. Five residues in the, N-terminal region were substituted by the corresponding amino acids of the, bovine seminal RNase. In addition, a Pro to Ser mutation was present at, position 50. The substitution of part of the N terminus has been critical, both in improving the expression of this enzyme as a recombinant protein, and in achieving its crystallisation. The determination of the crystal, structure revealed the characteristic RNase fold including a V-shaped, beta-sheet and three alpha-helices. It differs from its bovine RNase, orthologue mainly in the loop regions. The active-site cleft shows a, similar architecture to that of its bovine counterpart, with the essential, residues occupying equivalent positions. In the present structure, however, His119 is displaced as it is in the structure of RNase A at high, pH. An interaction model of human ribonuclease with the ribonuclease, inhibitor, together with inhibition assays, indicate that, in contrast to, RNase A, the modification of the loop beta4beta5 is not enough to avoid, inhibition. This study represents the first crystallographic approach to, the human enzyme, and should constitute an invaluable tool for the design, of ribonuclease variants with acquired cytotoxic properties.
<StructureSection load='1dza' size='340' side='right'caption='[[1dza]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1dza]] 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=1DZA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DZA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FME:N-FORMYLMETHIONINE'>FME</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=1dza FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dza OCA], [https://pdbe.org/1dza PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dza RCSB], [https://www.ebi.ac.uk/pdbsum/1dza PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dza ProSAT]</span></td></tr>
</table>
== 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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dz/1dza_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1dza ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We have determined the crystal structure of a human pancreatic ribonuclease or RNase 1 variant at 1.65 A resolution. Five residues in the N-terminal region were substituted by the corresponding amino acids of the bovine seminal RNase. In addition, a Pro to Ser mutation was present at position 50. The substitution of part of the N terminus has been critical both in improving the expression of this enzyme as a recombinant protein and in achieving its crystallisation. The determination of the crystal structure revealed the characteristic RNase fold including a V-shaped beta-sheet and three alpha-helices. It differs from its bovine RNase orthologue mainly in the loop regions. The active-site cleft shows a similar architecture to that of its bovine counterpart, with the essential residues occupying equivalent positions. In the present structure, however, His119 is displaced as it is in the structure of RNase A at high pH. An interaction model of human ribonuclease with the ribonuclease inhibitor, together with inhibition assays, indicate that, in contrast to RNase A, the modification of the loop beta4beta5 is not enough to avoid inhibition. This study represents the first crystallographic approach to the human enzyme, and should constitute an invaluable tool for the design of ribonuclease variants with acquired cytotoxic properties.


==About this Structure==
Three-dimensional structure of a human pancreatic ribonuclease variant, a step forward in the design of cytotoxic ribonucleases.,Pous J, Canals A, Terzyan SS, Guasch A, Benito A, Ribo M, Vilanova M, Coll M J Mol Biol. 2000 Oct 13;303(1):49-60. PMID:11021969<ref>PMID:11021969</ref>
1DZA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Pancreatic_ribonuclease Pancreatic ribonuclease], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.27.5 3.1.27.5] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1DZA OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Three-dimensional structure of a human pancreatic ribonuclease variant, a step forward in the design of cytotoxic ribonucleases., Pous J, Canals A, Terzyan SS, Guasch A, Benito A, Ribo M, Vilanova M, Coll M, J Mol Biol. 2000 Oct 13;303(1):49-60. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11021969 11021969]
</div>
<div class="pdbe-citations 1dza" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Ribonuclease 3D structures|Ribonuclease 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Pancreatic ribonuclease]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Benito A]]
[[Category: Benito, A.]]
[[Category: Canals A]]
[[Category: Canals, A.]]
[[Category: Coll M]]
[[Category: Coll, M.]]
[[Category: Guasch A]]
[[Category: Guasch, A.]]
[[Category: Pous J]]
[[Category: Pous, J.]]
[[Category: Ribo M]]
[[Category: Ribo, M.]]
[[Category: Terzyan SS]]
[[Category: Terzyan, S.S.]]
[[Category: Vilanova M]]
[[Category: Vilanova, M.]]
[[Category: human pancreatic ribonuclease]]
[[Category: ribonuclease]]
[[Category: rnase]]
 
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