2fak: Difference between revisions

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-[[Image:2fak.gif|left|200px]]<br /><applet load="2fak" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="2fak, resolution 2.80&Aring;" />
-'''Crystal structure of Salinosporamide A in complex with the yeast 20S proteasome'''<br />
-==Overview==
+==Crystal structure of Salinosporamide A in complex with the yeast 20S proteasome==
-The crystal structures of the yeast 20S proteasome core particle (CP) in, complex with Salinosporamides A (NPI-0052; 1) and B (4) were solved at &lt;3, angstroms resolution. Each ligand is covalently bound to Thr1O(gamma) via, an ester linkage to the carbonyl derived from the beta-lactone ring of the, inhibitor. In the case of 1, nucleophilic addition to the beta-lactone, ring is followed by addition of C-3O to the chloroethyl group, giving rise, to a cyclic ether. The crystal structures were compared to that of the, omuralide/CP structure solved previously, and the collective data provide, new insights into the mechanism of inhibition and irreversible binding of, 1. Upon opening of the beta-lactone ring, C-3O assumes the position, occupied by a water molecule in the unligated enzyme and hinders, deacylation of the enzyme-ligand complex. Furthermore, the resulting, protonation state of Thr1NH2 deactivates the catalytic N-terminus.
+<StructureSection load='2fak' size='340' side='right'caption='[[2fak]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2fak]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FAK FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SA1:(3AR,6R,6AS)-6-((S)-((S)-CYCLOHEX-2-ENYL)(HYDROXY)METHYL)-6A-METHYL-4-OXO-HEXAHYDRO-2H-FURO[3,2-C]PYRROLE-6-CARBALDEHYDE'>SA1</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=2fak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fak OCA], [https://pdbe.org/2fak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fak RCSB], [https://www.ebi.ac.uk/pdbsum/2fak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fak ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PSA2_YEAST PSA2_YEAST] The proteasome degrades poly-ubiquitinated proteins in the cytoplasm and in the nucleus. It is essential for the regulated turnover of proteins and for the removal of misfolded proteins. The proteasome is a multicatalytic proteinase complex that is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. It has an ATP-dependent proteolytic activity.
+== 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/fa/2fak_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=2fak ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The crystal structures of the yeast 20S proteasome core particle (CP) in complex with Salinosporamides A (NPI-0052; 1) and B (4) were solved at &lt;3 angstroms resolution. Each ligand is covalently bound to Thr1O(gamma) via an ester linkage to the carbonyl derived from the beta-lactone ring of the inhibitor. In the case of 1, nucleophilic addition to the beta-lactone ring is followed by addition of C-3O to the chloroethyl group, giving rise to a cyclic ether. The crystal structures were compared to that of the omuralide/CP structure solved previously, and the collective data provide new insights into the mechanism of inhibition and irreversible binding of 1. Upon opening of the beta-lactone ring, C-3O assumes the position occupied by a water molecule in the unligated enzyme and hinders deacylation of the enzyme-ligand complex. Furthermore, the resulting protonation state of Thr1NH2 deactivates the catalytic N-terminus.
-==About this Structure==
+Crystal structures of Salinosporamide A (NPI-0052) and B (NPI-0047) in complex with the 20S proteasome reveal important consequences of beta-lactone ring opening and a mechanism for irreversible binding.,Groll M, Huber R, Potts BC J Am Chem Soc. 2006 Apr 19;128(15):5136-41. PMID:16608349<ref>PMID:16608349</ref>
-FAK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with SA1 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Proteasome_endopeptidase_complex Proteasome endopeptidase complex], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.25.1 3.4.25.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FAK OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-Crystal structures of Salinosporamide A (NPI-0052) and B (NPI-0047) in complex with the 20S proteasome reveal important consequences of beta-lactone ring opening and a mechanism for irreversible binding., Groll M, Huber R, Potts BC, J Am Chem Soc. 2006 Apr 19;128(15):5136-41. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16608349 16608349]
+</div>
-[[Category: Proteasome endopeptidase complex]]
+<div class="pdbe-citations 2fak" style="background-color:#fffaf0;"></div>
-[[Category: Protein complex]]
+==See Also==
+*[[Proteasome 3D structures|Proteasome 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Saccharomyces cerevisiae]]
-[[Category: Groll, M.]]
+[[Category: Groll M]]
-[[Category: Potts, B.C.]]
+[[Category: Potts BC]]
-[[Category: SA1]]
-[[Category: drug design]]
-[[Category: inhibitor]]
-[[Category: protease]]
-[[Category: proteasome]]
-[[Category: ubiquitin]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 10:27:22 2007''