5dl1: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
''' | ==ClpP from Staphylococcus aureus in complex with AV145== | ||
<StructureSection load='5dl1' size='340' side='right' caption='[[5dl1]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5dl1]] is a 14 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DL1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DL1 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5C2:1-(PROPAN-2-YL)-N-{[2-(THIOPHEN-2-YL)-1,3-OXAZOL-4-YL]METHYL}-1H-PYRAZOLO[3,4-B]PYRIDINE-5-CARBOXAMIDE'>5C2</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3v5e|3v5e]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5dl1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dl1 OCA], [http://pdbe.org/5dl1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dl1 RCSB], [http://www.ebi.ac.uk/pdbsum/5dl1 PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/CLPP_STAAB CLPP_STAAB]] 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. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Caseinolytic protease P (ClpP) is an important regulator of Staphylococcus aureus pathogenesis. A high-throughput screening for inhibitors of ClpP peptidase activity led to the identification of the first non-covalent binder for this enzyme class. Co-crystallization of the small molecule with S. aureus ClpP revealed a novel binding mode: Because of the rotation of the conserved residue proline 125, ClpP is locked in a defined conformational state, which results in distortion of the catalytic triad and inhibition of the peptidase activity. Based on these structural insights, the molecule was optimized by rational design and virtual screening, resulting in derivatives exceeding the potency of previous ClpP inhibitors. Strikingly, the conformational lock is overturned by binding of ClpX, an associated chaperone that enables proteolysis by substrate unfolding in the ClpXP complex. Thus, regulation of inhibitor binding by associated chaperones is an unexpected mechanism important for ClpP drug development. | |||
Reversible Inhibitors Arrest ClpP in a Defined Conformational State that Can Be Revoked by ClpX Association.,Pahl A, Lakemeyer M, Vielberg MT, Hackl MW, Vomacka J, Korotkov VS, Stein ML, Fetzer C, Lorenz-Baath K, Richter K, Waldmann H, Groll M, Sieber SA Angew Chem Int Ed Engl. 2015 Nov 13. doi: 10.1002/anie.201507266. PMID:26566002<ref>PMID:26566002</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5dl1" style="background-color:#fffaf0;"></div> | |||
== References == | |||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Endopeptidase Clp]] | |||
[[Category: Groll, M]] | [[Category: Groll, M]] | ||
[[Category: Vielberg, M T]] | |||
[[Category: Allosteric regulation]] | |||
[[Category: Binding analysis]] | |||
[[Category: Caseinolytic protease]] | |||
[[Category: Hydrolase]] | |||
[[Category: Hydrolase-hydrolase inhibitor complex]] | |||