9b06: Difference between revisions

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-'''Unreleased structure'''
-The entry 9b06 is ON HOLD  until Paper Publication
+==Mycolicibacterium smegmatis ClpS with LeuThr dipeptide and Mg2+==
+<StructureSection load='9b06' size='340' side='right'caption='[[9b06]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9b06]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9B06 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9B06 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LCZ:(2S)-2-AMINO-4-METHYLPENTANAL'>LCZ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=THR:THREONINE'>THR</scene></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=9b06 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9b06 OCA], [https://pdbe.org/9b06 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9b06 RCSB], [https://www.ebi.ac.uk/pdbsum/9b06 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9b06 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/A0R1X7_MYCS2 A0R1X7_MYCS2] Involved in the modulation of the specificity of the ClpAP-mediated ATP-dependent protein degradation.[HAMAP-Rule:MF_00302]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Drug-resistant tuberculosis infections are a major threat to global public health. The essential mycobacterial ClpC1P1P2 protease has received attention as a prospective target for novel antibacterial therapeutics. However, efforts to probe its function in cells are constrained by our limited knowledge of its physiological proteolytic repertoire. Here, we interrogate the role of mycobacterial ClpS in directing N-degron pathway proteolysis by ClpC1P1P2 in Mycolicibacterium smegmatis. Binding assays demonstrate that mycobacterial ClpS binds canonical primary destabilizing residues (Leu, Phe, Tyr, Trp) with moderate affinity. N-degron binding restricts the conformational flexibility of a loop adjacent to the ClpS N-degron binding pocket and strengthens ClpS*ClpC1 binding affinity ~30-fold, providing a mechanism for cells to prioritize N-degron proteolysis when substrates are abundant. Proteolytic reporter assays in M. smegmatis confirm degradation of substrates bearing primary N-degrons, but suggest that secondary N-degrons are absent in mycobacteria. This work expands our understanding of the mycobacterial N-degron pathway and identifies ClpS as a critical component for substrate specificity, providing insights that may support the development of improved Clp protease inhibitors.
-Authors: Presloid, C.J., Jiang, J., Beardslee, P.C., Anderson, H.R., Swayne, T.M., Schmitz, K.R.
+ClpS Directs Degradation of N-Degron Substrates With Primary Destabilizing Residues in Mycolicibacterium smegmatis.,Presloid CJ, Jiang J, Kandel P, Anderson HR, Beardslee PC, Swayne TM, Schmitz KR Mol Microbiol. 2024 Dec 3. doi: 10.1111/mmi.15334. PMID:39626090<ref>PMID:39626090</ref>
-Description: Mycolicibacterium smegmatis ClpS with LeuThr dipeptide and Mg2+
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Anderson, H.R]]
+<div class="pdbe-citations 9b06" style="background-color:#fffaf0;"></div>
-[[Category: Presloid, C.J]]
+== References ==
-[[Category: Swayne, T.M]]
+<references/>
-[[Category: Beardslee, P.C]]
+__TOC__
-[[Category: Schmitz, K.R]]
+</StructureSection>
-[[Category: Jiang, J]]
+[[Category: Large Structures]]
+[[Category: Mycolicibacterium smegmatis MC2 155]]
+[[Category: Anderson HR]]
+[[Category: Beardslee PC]]
+[[Category: Jiang J]]
+[[Category: Presloid CJ]]
+[[Category: Schmitz KR]]
+[[Category: Swayne TM]]