6ew9
From Proteopedia
CRYSTAL STRUCTURE OF DEGS STRESS SENSOR PROTEASE IN COMPLEX WITH ACTIVATING DNRLGLVYQF PEPTIDE
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 PubMedCovalent 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
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Categories: Ecoli | Peptidase Do | Porfetye, A T | Stege, P | Vetter, I R | Activator peptide | Hydrolase | Pdz | Periplasm | Protease | Serine proteiase | Stress-sensor
