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| | ==Crystal Structure of M. tuberculosis ClpP1P2 bound to ADEP and agonist== | | ==Crystal Structure of M. tuberculosis ClpP1P2 bound to ADEP and agonist== |
| - | <StructureSection load='4u0g' size='340' side='right' caption='[[4u0g]], [[Resolution|resolution]] 3.20Å' scene=''> | + | <StructureSection load='4u0g' size='340' side='right'caption='[[4u0g]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4u0g]] is a 42 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U0G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U0G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4u0g]] is a 42 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U0G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U0G FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZIL:N-[(BENZYLOXY)CARBONYL]-L-ISOLEUCYL-L-LEUCINE'>ZIL</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]] 3.1978Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=39Y:(2E,5S)-5-METHYLHEPT-2-ENOIC+ACID'>39Y</scene>, <scene name='pdbligand=3A0:(2S,4S)-4-METHYLPIPERIDINE-2-CARBOXYLIC+ACID'>3A0</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=WFP:3,5-DIFLUORO-L-PHENYLALANINE'>WFP</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=39Y:(2E,5S)-5-METHYLHEPT-2-ENOIC+ACID'>39Y</scene>, <scene name='pdbligand=3A0:(2S,4S)-4-METHYLPIPERIDINE-2-CARBOXYLIC+ACID'>3A0</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=WFP:3,5-DIFLUORO-L-PHENYLALANINE'>WFP</scene>, <scene name='pdbligand=ZIL:N-[(BENZYLOXY)CARBONYL]-L-ISOLEUCYL-L-LEUCINE'>ZIL</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=4u0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u0g OCA], [https://pdbe.org/4u0g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u0g RCSB], [https://www.ebi.ac.uk/pdbsum/4u0g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u0g 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=4u0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u0g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u0g RCSB], [http://www.ebi.ac.uk/pdbsum/4u0g PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CLPP2_MYCTU CLPP2_MYCTU]] 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). Degrades anti-sigma-D factor RsdA when present in a complex with ClpP1 and ClpX. Degrades anti-sigma-E factor RseA in the presence of ClpC1. Does not seem to act on anti-sigma-L factor RslA.[HAMAP-Rule:MF_00444]<ref>PMID:20025669</ref> <ref>PMID:23314154</ref> [[http://www.uniprot.org/uniprot/CLPP1_MYCTU CLPP1_MYCTU]] 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/CLPP2_MYCTU CLPP2_MYCTU] 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). Degrades anti-sigma-D factor RsdA when present in a complex with ClpP1 and ClpX. Degrades anti-sigma-E factor RseA in the presence of ClpC1. Does not seem to act on anti-sigma-L factor RslA.[HAMAP-Rule:MF_00444]<ref>PMID:20025669</ref> <ref>PMID:23314154</ref> |
| | <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 4u0g" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Clp protease 3D structures|Clp protease 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Endopeptidase Clp]] | + | [[Category: Large Structures]] |
| - | [[Category: Carney, D W]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Sauer, R T]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Schmitz, K R]] | + | [[Category: Carney DW]] |
| - | [[Category: Sello, J K]] | + | [[Category: Sauer RT]] |
| - | [[Category: Hydrolase]] | + | [[Category: Schmitz KR]] |
| - | [[Category: Hydrolase-antibiotic complex]] | + | [[Category: Sello JK]] |
| - | [[Category: Peptidase]]
| + | |
| Structural highlights
4u0g is a 42 chain structure with sequence from Mycobacterium tuberculosis H37Rv and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 3.1978Å |
| Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
CLPP2_MYCTU 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). Degrades anti-sigma-D factor RsdA when present in a complex with ClpP1 and ClpX. Degrades anti-sigma-E factor RseA in the presence of ClpC1. Does not seem to act on anti-sigma-L factor RslA.[HAMAP-Rule:MF_00444][1] [2]
Publication Abstract from PubMed
Caseinolytic peptidase P (ClpP), a double-ring peptidase with 14 subunits, collaborates with ATPases associated with diverse activities (AAA+) partners to execute ATP-dependent protein degradation. Although many ClpP enzymes self-assemble into catalytically active homo-tetradecamers able to cleave small peptides, the Mycobacterium tuberculosis enzyme consists of discrete ClpP1 and ClpP2 heptamers that require a AAA+ partner and protein-substrate delivery or a peptide agonist to stabilize assembly of the active tetradecamer. Here, we show that cyclic acyldepsipeptides (ADEPs) and agonist peptides synergistically activate ClpP1P2 by mimicking AAA+ partners and substrates, respectively, and determine the structure of the activated complex. Our studies establish the basis of heteromeric ClpP1P2 assembly and function, reveal tight coupling between the conformations of each ring, show that ADEPs bind only to one ring but appear to open the axial pores of both rings, provide a foundation for rational drug development, and suggest strategies for studying the roles of individual ClpP1 and ClpP2 rings in Clp-family proteolysis.
Crystal structure of Mycobacterium tuberculosis ClpP1P2 suggests a model for peptidase activation by AAA+ partner binding and substrate delivery.,Schmitz KR, Carney DW, Sello JK, Sauer RT Proc Natl Acad Sci U S A. 2014 Sep 29. pii: 201417120. PMID:25267638[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Barik S, Sureka K, Mukherjee P, Basu J, Kundu M. RseA, the SigE specific anti-sigma factor of Mycobacterium tuberculosis, is inactivated by phosphorylation-dependent ClpC1P2 proteolysis. Mol Microbiol. 2010 Feb;75(3):592-606. doi: 10.1111/j.1365-2958.2009.07008.x., Epub 2009 Dec 16. PMID:20025669 doi:http://dx.doi.org/10.1111/j.1365-2958.2009.07008.x
- ↑ Jaiswal RK, Prabha TS, Manjeera G, Gopal B. Mycobacterium tuberculosis RsdA provides a conformational rationale for selective regulation of sigma-factor activity by proteolysis. Nucleic Acids Res. 2013 Jan 11. PMID:23314154 doi:http://dx.doi.org/10.1093/nar/gks1468
- ↑ Schmitz KR, Carney DW, Sello JK, Sauer RT. Crystal structure of Mycobacterium tuberculosis ClpP1P2 suggests a model for peptidase activation by AAA+ partner binding and substrate delivery. Proc Natl Acad Sci U S A. 2014 Sep 29. pii: 201417120. PMID:25267638 doi:http://dx.doi.org/10.1073/pnas.1417120111
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