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| | <StructureSection load='6n80' size='340' side='right'caption='[[6n80]], [[Resolution|resolution]] 1.96Å' scene=''> | | <StructureSection load='6n80' size='340' side='right'caption='[[6n80]], [[Resolution|resolution]] 1.96Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6n80]] is a 14 chain structure with sequence from [http://en.wikipedia.org/wiki/Staa8 Staa8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N80 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N80 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6n80]] is a 14 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_NCTC_8325 Staphylococcus aureus subsp. aureus NCTC 8325]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N80 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6N80 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JT7:N-[(1R)-1-borono-3-methylbutyl]-N~2~-(2-chloro-4-methoxybenzene-1-carbonyl)-L-leucinamide'>JT7</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]] 1.96Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">clpP, SAOUHSC_00790 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=93061 STAA8])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JT7:N-[(1R)-1-borono-3-methylbutyl]-N~2~-(2-chloro-4-methoxybenzene-1-carbonyl)-L-leucinamide'>JT7</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Endopeptidase_Clp Endopeptidase Clp], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.92 3.4.21.92] </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=6n80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n80 OCA], [https://pdbe.org/6n80 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6n80 RCSB], [https://www.ebi.ac.uk/pdbsum/6n80 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6n80 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=6n80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n80 OCA], [http://pdbe.org/6n80 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n80 RCSB], [http://www.ebi.ac.uk/pdbsum/6n80 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n80 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CLPP_STAA8 CLPP_STAA8]] Cleaves peptides in various proteins in a process that requires ATP hydrolysis. Has a chymotrypsin-like activity. Plays a major role in the degradation of misfolded proteins (By similarity). | + | [https://www.uniprot.org/uniprot/CLPP_STAA8 CLPP_STAA8] Cleaves peptides in various proteins in a process that requires ATP hydrolysis. Has a chymotrypsin-like activity. Plays a major role in the degradation of misfolded proteins (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Endopeptidase Clp]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Staa8]] | + | [[Category: Staphylococcus aureus subsp. aureus NCTC 8325]] |
| - | [[Category: Griffith, E C]] | + | [[Category: Griffith EC]] |
| - | [[Category: Lee, R E]] | + | [[Category: Lee RE]] |
| - | [[Category: Clpp]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
CLPP_STAA8 Cleaves peptides in various proteins in a process that requires ATP hydrolysis. Has a chymotrypsin-like activity. Plays a major role in the degradation of misfolded proteins (By similarity).
Publication Abstract from PubMed
Boronic acids have attracted the attention of synthetic and medicinal chemists due to boron's ability to modulate enzyme function. Recently, we demonstrated that boron-containing amphoteric building blocks facilitate the discovery of bioactive aminoboronic acids. Herein, we have augmented this capability with a de novo library design and virtural screening platform modified for covalent ligands. This technique has allowed us to rapidly design and identify a series of alpha-aminoboronic acids as the first inhibitors of human ClpXP, which is responsible for the degradation of misfolded proteins.
De novo design of boron-based peptidomimetics as potent inhibitors of human ClpP in the presence of human ClpX.,Tan J, Grouleff JG, Jitkova Y, Diaz DB, Griffith E, Shao W, Bogdanchikova AF, Poda G, Schimmer AD, Lee RE, Yudin AK J Med Chem. 2019 Jun 12. doi: 10.1021/acs.jmedchem.9b00878. PMID:31187989[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tan J, Grouleff JG, Jitkova Y, Diaz DB, Griffith E, Shao W, Bogdanchikova AF, Poda G, Schimmer AD, Lee RE, Yudin AK. De novo design of boron-based peptidomimetics as potent inhibitors of human ClpP in the presence of human ClpX. J Med Chem. 2019 Jun 12. doi: 10.1021/acs.jmedchem.9b00878. PMID:31187989 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b00878
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