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| | ==Caseinolytic protease (ClpP) from Staphylococcus aureus mutant - V7A== | | ==Caseinolytic protease (ClpP) from Staphylococcus aureus mutant - V7A== |
| - | <StructureSection load='6dkf' size='340' side='right' caption='[[6dkf]], [[Resolution|resolution]] 3.70Å' scene=''> | + | <SX load='6dkf' size='340' side='right' viewer='molstar' caption='[[6dkf]], [[Resolution|resolution]] 3.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6dkf]] is a 14 chain structure with sequence from [http://en.wikipedia.org/wiki/Staae Staae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DKF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DKF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6dkf]] is a 14 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_str._Newman Staphylococcus aureus subsp. aureus str. Newman]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DKF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DKF FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">clpP, NWMN_0736 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=426430 STAAE])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.7Å</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=6dkf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dkf OCA], [https://pdbe.org/6dkf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dkf RCSB], [https://www.ebi.ac.uk/pdbsum/6dkf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dkf 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=6dkf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dkf OCA], [http://pdbe.org/6dkf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dkf RCSB], [http://www.ebi.ac.uk/pdbsum/6dkf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dkf ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CLPP_STAAE CLPP_STAAE]] 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. | + | [https://www.uniprot.org/uniprot/CLPP_STAAE CLPP_STAAE] 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;">
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| - | == Publication Abstract from PubMed ==
| + | |
| - | Protein homeostasis is critically important for cell viability. Key to this process is the refolding of misfolded or aggregated proteins by molecular chaperones or, alternatively, their degradation by proteases. In most prokaryotes and in chloroplasts and mitochondria, protein degradation is performed by the caseinolytic protease ClpP, a tetradecamer barrel-like proteolytic complex. Dysregulating ClpP function has shown promise in fighting antibiotic resistance and as a potential therapy for acute myeloid leukemia. Here we use methyl-transverse relaxation-optimized spectroscopy (TROSY)-based NMR, cryo-EM, biochemical assays, and molecular dynamics simulations to characterize the structural dynamics of ClpP from Staphylococcus aureus (SaClpP) in wild-type and mutant forms in an effort to discover conformational hotspots that regulate its function. Wild-type SaClpP was found exclusively in the active extended form, with the N-terminal domains of its component protomers in predominantly beta-hairpin conformations that are less well-defined than other regions of the protein. A hydrophobic site was identified that, upon mutation, leads to unfolding of the N-terminal domains, loss of SaClpP activity, and formation of a previously unobserved split-ring conformation with a pair of 20-A-wide pores in the side of the complex. The extended form of the structure and partial activity can be restored via binding of ADEP small-molecule activators. The observed structural plasticity of the N-terminal gates is shown to be a conserved feature through studies of Escherichia coli and Neisseria meningitidis ClpP, suggesting a potential avenue for the development of molecules to allosterically modulate the function of ClpP.
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| - | Reversible inhibition of the ClpP protease via an N-terminal conformational switch.,Vahidi S, Ripstein ZA, Bonomi M, Yuwen T, Mabanglo MF, Juravsky JB, Rizzolo K, Velyvis A, Houry WA, Vendruscolo M, Rubinstein JL, Kay LE Proc Natl Acad Sci U S A. 2018 Jun 25. pii: 1805125115. doi:, 10.1073/pnas.1805125115. PMID:29941580<ref>PMID:29941580</ref>
| + | ==See Also== |
| - | | + | *[[Clp protease 3D structures|Clp protease 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6dkf" style="background-color:#fffaf0;"></div>
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| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| - | </StructureSection> | + | </SX> |
| - | [[Category: Endopeptidase Clp]] | + | [[Category: Large Structures]] |
| - | [[Category: Staae]] | + | [[Category: Staphylococcus aureus subsp. aureus str. Newman]] |
| - | [[Category: Kay, L E]] | + | [[Category: Kay LE]] |
| - | [[Category: Ripstein, Z A]] | + | [[Category: Ripstein ZA]] |
| - | [[Category: Rubinstein, J L]] | + | [[Category: Rubinstein JL]] |
| - | [[Category: Vahidi, S]] | + | [[Category: Vahidi S]] |
| - | [[Category: Hydrolase]]
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| - | [[Category: Protease]]
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