5dzk
From Proteopedia
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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='5dzk' size='340' side='right' caption='[[5dzk]], [[Resolution|resolution]] 3.07Å' scene=''> | + | <StructureSection load='5dzk' size='340' side='right'caption='[[5dzk]], [[Resolution|resolution]] 3.07Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5dzk]] is a 56 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DZK OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5dzk]] is a 56 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_CDC1551 Mycobacterium tuberculosis CDC1551] 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=5DZK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DZK FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.07Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEZ:BENZOIC+ACID'>BEZ</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5dzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dzk OCA], [https://pdbe.org/5dzk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dzk RCSB], [https://www.ebi.ac.uk/pdbsum/5dzk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dzk ProSAT]</span></td></tr> |
</table> | </table> | ||
| - | {{Large structure}} | ||
== Function == | == Function == | ||
| - | [ | + | [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;"> | ||
| + | == 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<ref>PMID:26858247</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5dzk" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Clp protease 3D structures|Clp protease 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Mycobacterium tuberculosis CDC1551]] |
| - | [[Category: | + | [[Category: Synthetic construct]] |
| - | [[Category: | + | [[Category: LI M]] |
| - | [[Category: | + | [[Category: Maurizi M]] |
| + | [[Category: Wlodawer A]] | ||
Current revision
Crystal structure of the active form of the proteolytic complex clpP1 and clpP2
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