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| - | {{Large structure}}
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| | ==crystal structure of the active form of the proteolytic complex clpP1 and clpP2== | | ==crystal structure of the active form of the proteolytic complex clpP1 and clpP2== |
| - | <StructureSection load='5e0s' size='340' side='right' caption='[[5e0s]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='5e0s' size='340' side='right'caption='[[5e0s]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5e0s]] is a 28 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E0S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E0S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5e0s]] is a 28 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_CDC1551 Mycobacterium tuberculosis CDC1551]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E0S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5E0S FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9Å</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=5e0s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e0s OCA], [http://pdbe.org/5e0s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e0s RCSB], [http://www.ebi.ac.uk/pdbsum/5e0s PDBsum]</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=5e0s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e0s OCA], [https://pdbe.org/5e0s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5e0s RCSB], [https://www.ebi.ac.uk/pdbsum/5e0s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5e0s ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | {{Large structure}} | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CLPP2_MYCTO CLPP2_MYCTO]] 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.[HAMAP-Rule:MF_00444] [[http://www.uniprot.org/uniprot/CLPP1_MYCTO CLPP1_MYCTO]] 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.[HAMAP-Rule:MF_00444] | + | [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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| | </div> | | </div> |
| | <div class="pdbe-citations 5e0s" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5e0s" 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: LI, M]] | + | [[Category: Mycobacterium tuberculosis CDC1551]] |
| - | [[Category: Maurizi, M]] | + | [[Category: LI M]] |
| - | [[Category: Wlodawer, A]] | + | [[Category: Maurizi M]] |
| - | [[Category: Hydrolase]] | + | [[Category: Wlodawer A]] |
| Structural highlights
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
The ClpP protease complex and its regulatory ATPases, ClpC1 and ClpX, in Mycobacterium tuberculosis (Mtb) are essential and therefore promising drug targets. The Mtb ClpP protease consists of two heptameric rings, one composed of ClpP1 and one of ClpP2 subunits. Formation of the enzymatically active ClpP1P2 complex requires binding of N-blocked dipeptide activators. We have found a new potent activator (benzoyl-leucine-leucine (Bz-LL)) that binds more tightly and stimulates its peptidase activity 3-4-fold more than previous activators. Bz-LL-activated ClpP1P2 stimulated specifically the ATPase activity of Mtb ClpC1 or ClpX, and the resulting holoenzyme complexes exhibit 2-3-fold enhanced ATPase activity, peptide cleavage and ATP-dependent protein degradation. The crystal structure of ClpP1P2 with bound Bz-LL was determined at a resolution of 3.07 A and with benzyloxy carbonyl (Z)-LL bound at 2.9 A. Bz-LL is present in all 14 active sites, whereas no Z-LL density was visible. Surprisingly, Bz-LL adopts opposite orientations in ClpP1 and ClpP2. In ClpP1, Bz-LL binds with the C-terminal leucine side chain in the S1 pocket. One carboxy-terminal oxygen is close to the catalytic serine, while the other contacts backbone amides in the oxyanion hole. In ClpP2, Bz-LL binds with the benzoyl group in the S1 pocket and the peptide hydrogen bonded between parallel beta-strands. The ClpP2 axial loops are extended forming an open axial channel as was previously observed with bound ADEP antibiotics. Thus occupancy of the active sites of ClpP allosterically alters sites on the surfaces that affect the association of ClpP1 and ClpP2 rings, interactions with regulatory ATPases, and entry of protein substrates.
Structure and Functional Properties of the active form of the proteolytic complex, ClpP1P2 from Mycobacterium tuberculosis.,Li M, Kandror O, Akopian T, Dharkar P, Wlodawer A, Maurizi MR, Goldberg AL J Biol Chem. 2016 Feb 8. pii: jbc.M115.700344. PMID:26858247[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
- ↑ Li M, Kandror O, Akopian T, Dharkar P, Wlodawer A, Maurizi MR, Goldberg AL. Structure and Functional Properties of the active form of the proteolytic complex, ClpP1P2 from Mycobacterium tuberculosis. J Biol Chem. 2016 Feb 8. pii: jbc.M115.700344. PMID:26858247 doi:http://dx.doi.org/10.1074/jbc.M115.700344
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