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| | ==CRYSTAL STRUCTURE OF DEGS STRESS SENSOR PROTEASE IN COMPLEX WITH ACTIVATING DNRLGLVYQF PEPTIDE== | | ==CRYSTAL STRUCTURE OF DEGS STRESS SENSOR PROTEASE IN COMPLEX WITH ACTIVATING DNRLGLVYQF PEPTIDE== |
| - | <StructureSection load='6ew9' size='340' side='right' caption='[[6ew9]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='6ew9' size='340' side='right'caption='[[6ew9]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ew9]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EW9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EW9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ew9]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] 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=6EW9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EW9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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]] 2.2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">degS, hhoB, htrH, b3235, JW3204 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidase_Do Peptidase Do], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.107 3.4.21.107] </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=6ew9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ew9 OCA], [https://pdbe.org/6ew9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ew9 RCSB], [https://www.ebi.ac.uk/pdbsum/6ew9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ew9 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=6ew9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ew9 OCA], [http://pdbe.org/6ew9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ew9 RCSB], [http://www.ebi.ac.uk/pdbsum/6ew9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ew9 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DEGS_ECOLI DEGS_ECOLI]] When heat shock or other environmental stresses disrupt protein folding in the periplasm, DegS senses the accumulation of unassembled outer membrane porins (OMPs) and then initiates RseA (anti sigma-E factor) degradation by cleaving it in its periplasmic domain, making it an attractive substrate for subsequent cleavage by RseP. This cascade that ultimately leads to the sigma-E-driven expression of a variety of factors dealing with folding stress in the periplasm and OMP assembly.<ref>PMID:12183369</ref> <ref>PMID:19695325</ref> | + | [https://www.uniprot.org/uniprot/DEGS_ECOLI DEGS_ECOLI] When heat shock or other environmental stresses disrupt protein folding in the periplasm, DegS senses the accumulation of unassembled outer membrane porins (OMPs) and then initiates RseA (anti sigma-E factor) degradation by cleaving it in its periplasmic domain, making it an attractive substrate for subsequent cleavage by RseP. This cascade that ultimately leads to the sigma-E-driven expression of a variety of factors dealing with folding stress in the periplasm and OMP assembly.<ref>PMID:12183369</ref> <ref>PMID:19695325</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Peptidase Do]] | + | [[Category: Large Structures]] |
| - | [[Category: Porfetye, A T]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Stege, P]] | + | [[Category: Porfetye AT]] |
| - | [[Category: Vetter, I R]] | + | [[Category: Stege P]] |
| - | [[Category: Activator peptide]] | + | [[Category: Vetter IR]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Pdz]]
| + | |
| - | [[Category: Periplasm]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Serine proteiase]]
| + | |
| - | [[Category: Stress-sensor]]
| + | |
| Structural highlights
Function
DEGS_ECOLI When heat shock or other environmental stresses disrupt protein folding in the periplasm, DegS senses the accumulation of unassembled outer membrane porins (OMPs) and then initiates RseA (anti sigma-E factor) degradation by cleaving it in its periplasmic domain, making it an attractive substrate for subsequent cleavage by RseP. This cascade that ultimately leads to the sigma-E-driven expression of a variety of factors dealing with folding stress in the periplasm and OMP assembly.[1] [2]
Publication Abstract from PubMed
Covalent modifications of nonactive site lysine residues by small molecule probes has recently evolved into an important strategy for interrogating biological systems. Here, we report the discovery of a class of bioreactive compounds that covalently modify lysine residues in DegS, the rate limiting protease of the essential bacterial outer membrane stress response pathway. These modifications lead to an allosteric activation and allow the identification of novel residues involved in the allosteric activation circuit. These findings were validated by structural analyses via X-ray crystallography and cell-based reporter systems. We anticipate that our findings are not only relevant for a deeper understanding of the structural basis of allosteric activation in DegS and other HtrA serine proteases but also pinpoint an alternative use of covalent small molecules for probing essential biochemical mechanisms.
Identification of Noncatalytic Lysine Residues from Allosteric Circuits via Covalent Probes.,Bongard J, Lorenz M, Vetter IR, Stege P, Porfetye AT, Schmitz AL, Kaschani F, Wolf A, Koch U, Nussbaumer P, Klebl B, Kaiser M, Ehrmann M ACS Chem Biol. 2018 Apr 16. doi: 10.1021/acschembio.8b00101. PMID:29658704[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Alba BM, Leeds JA, Onufryk C, Lu CZ, Gross CA. DegS and YaeL participate sequentially in the cleavage of RseA to activate the sigma(E)-dependent extracytoplasmic stress response. Genes Dev. 2002 Aug 15;16(16):2156-68. PMID:12183369 doi:10.1101/gad.1008902
- ↑ Meltzer M, Hasenbein S, Mamant N, Merdanovic M, Poepsel S, Hauske P, Kaiser M, Huber R, Krojer T, Clausen T, Ehrmann M. Structure, function and regulation of the conserved serine proteases DegP and DegS of Escherichia coli. Res Microbiol. 2009 Nov;160(9):660-6. doi: 10.1016/j.resmic.2009.07.012. Epub, 2009 Aug 18. PMID:19695325 doi:10.1016/j.resmic.2009.07.012
- ↑ Bongard J, Lorenz M, Vetter IR, Stege P, Porfetye AT, Schmitz AL, Kaschani F, Wolf A, Koch U, Nussbaumer P, Klebl B, Kaiser M, Ehrmann M. Identification of Noncatalytic Lysine Residues from Allosteric Circuits via Covalent Probes. ACS Chem Biol. 2018 Apr 16. doi: 10.1021/acschembio.8b00101. PMID:29658704 doi:http://dx.doi.org/10.1021/acschembio.8b00101
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