6EW9

CRYSTAL STRUCTURE OF DEGS STRESS SENSOR PROTEASE IN COMPLEX WITH ACTIVATING DNRLGLVYQF PEPTIDE

Summary for 6EW9

• Entry DOI: 10.2210/pdb6ew9/pdb
• Descriptor: Serine endoprotease DegS, DNRLGLVYQF PEPTIDE, DI(HYDROXYETHYL)ETHER, ... (5 entities in total)
• Functional Keywords: protease, stress-sensor, pdz, hydrolase, periplasm, serine proteiase, activator peptide
• Biological source: Escherichia coli K-12; More
• Total number of polymer chains: 6
• Total formula weight: 103902.76

Authors

Vetter, I.R.,Porfetye, A.T.,Stege, P. (deposition date: 2017-11-03, release date: 2018-04-25, Last modification date: 2024-05-08)

Primary citation

Bongard, J.,Lorenz, M.,Vetter, I.R.,Stege, P.,Porfetye, A.T.,Schmitz, A.L.,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., 13:1307-1312, 2018

PubMed Abstract: 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.

PubMed: 29658704
DOI: 10.1021/acschembio.8b00101

Experimental method

X-RAY DIFFRACTION (2.2 Å)