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| | ==20S yeast proteasome in complex with glidobactin== | | ==20S yeast proteasome in complex with glidobactin== |
| - | <StructureSection load='4fzg' size='340' side='right' caption='[[4fzg]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='4fzg' size='340' side='right'caption='[[4fzg]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fzg]] is a 32 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FZG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FZG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4fzg]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FZG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FZG FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=0W6:(4S)-4-AMINOPENTANOIC+ACID'>0W6</scene>, <scene name='pdbligand=LYO:4-HYDROXY-LYSINE'>LYO</scene>, <scene name='pdbligand=MH9:(2E,4E)-DODECA-2,4-DIENOIC+ACID'>MH9</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]] 3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ryp|1ryp]], [[2czy|2czy]], [[3bdm|3bdm]], [[4fzc|4fzc]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0W6:(4S)-4-AMINOPENTANOIC+ACID'>0W6</scene>, <scene name='pdbligand=LYO:4-HYDROXY-LYSINE'>LYO</scene>, <scene name='pdbligand=MH9:(2E,4E)-DODECA-2,4-DIENOIC+ACID'>MH9</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </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=4fzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fzg OCA], [https://pdbe.org/4fzg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fzg RCSB], [https://www.ebi.ac.uk/pdbsum/4fzg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fzg ProSAT]</span></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=4fzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fzg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fzg RCSB], [http://www.ebi.ac.uk/pdbsum/4fzg PDBsum]</span></td></tr> | + | |
| | </table> | | </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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4fzg" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Proteasome|Proteasome]] | + | *[[Proteasome 3D structures|Proteasome 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Proteasome endopeptidase complex]] | + | [[Category: Large Structures]] |
| - | [[Category: Saccharomyces cerevisiae]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Beck, P]] | + | [[Category: Beck P]] |
| - | [[Category: Becker, C F.W]] | + | [[Category: Becker CFW]] |
| - | [[Category: Dudler, R]] | + | [[Category: Dudler R]] |
| - | [[Category: Groll, M]] | + | [[Category: Groll M]] |
| - | [[Category: Kaiser, M]] | + | [[Category: Kaiser M]] |
| - | [[Category: Stein, M]] | + | [[Category: Stein M]] |
| - | [[Category: Drug development]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: N-terminal nucleophilic hydrolase]]
| + | |
| - | [[Category: Natural product]]
| + | |
| - | [[Category: Proteasome]]
| + | |
| - | [[Category: Protein degradation]]
| + | |
| - | [[Category: Ubiquitin]]
| + | |
| Structural highlights
Function
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.
Publication Abstract from PubMed
Natural products represent valuable lead structures for drug discovery. However, for most bioactive compounds no cellular target is yet identified and many substances predicted from genome analysis are inaccessible due to their life stage-dependent biosynthesis, which is not reflected in common isolation procedures. In response to these issues, an NMR-based and target-directed protease assay for inhibitor detection of the proteasome was developed. The methodology is suitable for one-shot identification of inhibitors in conglomerates and crude culture broths. The technique was applied for analysis of the different life stages of the bacterium Photorhabdus luminescens, which resulted in the isolation and characterization of cepafungin I (CepI), the strongest proteasome inhibitor described to date. Its biosynthesis is strictly regulated and solely induced by the specific environmental conditions determined by our methodology. The transferability of the developed technique to other drug targets may disclose an abundance of novel compounds applicable for drug development.
One-shot NMR analysis of microbial secretions identifies highly potent proteasome inhibitor.,Stein ML, Beck P, Kaiser M, Dudler R, Becker CF, Groll M Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18367-71. doi:, 10.1073/pnas.1211423109. Epub 2012 Oct 22. PMID:23091006[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Stein ML, Beck P, Kaiser M, Dudler R, Becker CF, Groll M. One-shot NMR analysis of microbial secretions identifies highly potent proteasome inhibitor. Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18367-71. doi:, 10.1073/pnas.1211423109. Epub 2012 Oct 22. PMID:23091006 doi:http://dx.doi.org/10.1073/pnas.1211423109
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