1r4y

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(New page: 200px<br /><applet load="1r4y" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r4y" /> '''SOLUTION STRUCTURE OF THE DELETION MUTANT DE...)
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[[Image:1r4y.jpg|left|200px]]<br /><applet load="1r4y" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1r4y" />
 
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'''SOLUTION STRUCTURE OF THE DELETION MUTANT DELTA(7-22) OF THE CYTOTOXIC RIBONUCLEASE ALPHA-SARCIN'''<br />
 
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==Overview==
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==SOLUTION STRUCTURE OF THE DELETION MUTANT DELTA(7-22) OF THE CYTOTOXIC RIBONUCLEASE ALPHA-SARCIN==
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The deletion mutant Delta(7-22) of alpha-sarcin, unlike its wild-type, protein counterpart, lacks the specific ability to degrade rRNA in intact, ribosomes and exhibits an increased unspecific ribonuclease activity and, decreased interaction with lipid vesicles. In trying to shed light on, these differences, we report here on the three-dimensional structure of, the Delta(7-22) alpha-sarcin mutant using NMR methods. We also evaluated, its dynamic properties on the basis of theoretical models and measured its, correlation time (6.2 nsec) by time-resolved fluorescence anisotropy. The, global fold characteristic of ribotoxins is preserved in the mutant. The, most significant differences with respect to the alpha-sarcin structure, are concentrated in (1) loop 2, (2) loop 3, which adopts a new, orientation, and (3) loop 5, which shows multiple conformations and an, altered dynamics. The interactions between loop 5 and the N-terminal, hairpin are lost in the mutant, producing increased solvent accessibility, of the active-site residues. The degree of solvent exposure of the, catalytic His 137 is similar to that shown by His 92 in RNase T1., Additionally, the calculated order parameters of residues belonging to, loop 5 in the mutant correspond to an internal dynamic behavior more, similar to RNase T1 than alpha-sarcin. On the other hand, changes in the, relative orientation of loop 3 move the lysine-rich region 111-114, crucial for substrate recognition, away from the active site. All of the, structural and dynamic data presented here reveal that the mutant is a, hybrid of ribotoxins and noncytotoxic ribonucleases, consistent with its, biological properties.
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<StructureSection load='1r4y' size='340' side='right'caption='[[1r4y]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1r4y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_giganteus Aspergillus giganteus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R4Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1R4Y FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 25 models</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1r4y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r4y OCA], [https://pdbe.org/1r4y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r4y RCSB], [https://www.ebi.ac.uk/pdbsum/1r4y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r4y ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/RNAS_ASPGI RNAS_ASPGI] Alpha-sarcin is specific for purines in both single- and double-stranded RNA. Its toxic action on eukaryotic cells is the result of cleavage of a single phosphodiester bond in the 60S subunit of ribosomes.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r4/1r4y_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1r4y ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The deletion mutant Delta(7-22) of alpha-sarcin, unlike its wild-type protein counterpart, lacks the specific ability to degrade rRNA in intact ribosomes and exhibits an increased unspecific ribonuclease activity and decreased interaction with lipid vesicles. In trying to shed light on these differences, we report here on the three-dimensional structure of the Delta(7-22) alpha-sarcin mutant using NMR methods. We also evaluated its dynamic properties on the basis of theoretical models and measured its correlation time (6.2 nsec) by time-resolved fluorescence anisotropy. The global fold characteristic of ribotoxins is preserved in the mutant. The most significant differences with respect to the alpha-sarcin structure are concentrated in (1) loop 2, (2) loop 3, which adopts a new orientation, and (3) loop 5, which shows multiple conformations and an altered dynamics. The interactions between loop 5 and the N-terminal hairpin are lost in the mutant, producing increased solvent accessibility of the active-site residues. The degree of solvent exposure of the catalytic His 137 is similar to that shown by His 92 in RNase T1. Additionally, the calculated order parameters of residues belonging to loop 5 in the mutant correspond to an internal dynamic behavior more similar to RNase T1 than alpha-sarcin. On the other hand, changes in the relative orientation of loop 3 move the lysine-rich region 111-114, crucial for substrate recognition, away from the active site. All of the structural and dynamic data presented here reveal that the mutant is a hybrid of ribotoxins and noncytotoxic ribonucleases, consistent with its biological properties.
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==About this Structure==
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NMR structure of the noncytotoxic alpha-sarcin mutant Delta(7-22): the importance of the native conformation of peripheral loops for activity.,Garcia-Mayoral MF, Garcia-Ortega L, Lillo MP, Santoro J, Martinez del Pozo A, Gavilanes JG, Rico M, Bruix M Protein Sci. 2004 Apr;13(4):1000-11. PMID:15044731<ref>PMID:15044731</ref>
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1R4Y is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Aspergillus_giganteus Aspergillus giganteus]. Active as [http://en.wikipedia.org/wiki/rRNA_endonuclease rRNA endonuclease], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.27.10 3.1.27.10] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1R4Y OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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NMR structure of the noncytotoxic alpha-sarcin mutant Delta(7-22): the importance of the native conformation of peripheral loops for activity., Garcia-Mayoral MF, Garcia-Ortega L, Lillo MP, Santoro J, Martinez del Pozo A, Gavilanes JG, Rico M, Bruix M, Protein Sci. 2004 Apr;13(4):1000-11. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15044731 15044731]
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</div>
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[[Category: Aspergillus giganteus]]
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<div class="pdbe-citations 1r4y" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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[[Category: rRNA endonuclease]]
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[[Category: Bruix, M.]]
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[[Category: Garcia-Mayoral, M.F.]]
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[[Category: Garcia-Ortega, L.]]
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[[Category: Gavilanes, J.G.]]
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[[Category: Lillo, M.P.]]
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[[Category: Pozo, A.Martinez.Del.]]
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[[Category: Rico, M.]]
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[[Category: Santoro, J.]]
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[[Category: alpha-beta protein]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 01:15:47 2007''
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==See Also==
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*[[Ribonuclease 3D structures|Ribonuclease 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Aspergillus giganteus]]
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[[Category: Large Structures]]
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[[Category: Bruix M]]
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[[Category: Garcia-Mayoral MF]]
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[[Category: Garcia-Ortega L]]
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[[Category: Gavilanes JG]]
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[[Category: Lillo MP]]
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[[Category: Martinez Del Pozo A]]
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[[Category: Rico M]]
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[[Category: Santoro J]]

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SOLUTION STRUCTURE OF THE DELETION MUTANT DELTA(7-22) OF THE CYTOTOXIC RIBONUCLEASE ALPHA-SARCIN

PDB ID 1r4y

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