6JJO

Crystal structure of the DegP dodecamer with a modulator


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 4.16 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.219 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Over-activation of a nonessential bacterial protease DegP as an antibiotic strategy

Cho, H.Choi, Y.Min, K.Son, J.B.Park, H.Lee, H.H.Kim, S.

(2020) Commun Biol 3: 547-547

  • DOI: https://doi.org/10.1038/s42003-020-01266-9
  • Primary Citation of Related Structures:  
    6JJK, 6JJL, 6JJO

  • PubMed Abstract: 

    Rising antibiotic resistance urgently begs for novel targets and strategies for antibiotic discovery. Here, we report that over-activation of the periplasmic DegP protease, a member of the highly conserved HtrA family, can be a viable strategy for antibiotic development. We demonstrate that tripodal peptidyl compounds that mimic DegP-activating lipoprotein variants allosterically activate DegP and inhibit the growth of an Escherichia coli strain with a permeable outer membrane in a DegP-dependent fashion. Interestingly, these compounds inhibit bacterial growth at a temperature at which DegP is not essential for cell viability, mainly by over-proteolysis of newly synthesized proteins. Co-crystal structures show that the peptidyl arms of the compounds bind to the substrate-binding sites of DegP. Overall, our results represent an intriguing example of killing bacteria by activating a non-essential enzyme, and thus expand the scope of antibiotic targets beyond the traditional essential proteins or pathways.


  • Organizational Affiliation

    Department of Chemistry, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Periplasmic serine endoprotease DegP
A, B, C, D, E
A, B, C, D, E, F
469Escherichia coli K-12Mutation(s): 1 
Gene Names: degPhtrAptdb0161JW0157
EC: 3.4.21.107
UniProt
Find proteins for P0C0V0 (Escherichia coli (strain K12))
Explore P0C0V0 
Go to UniProtKB:  P0C0V0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0C0V0
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
TMB-CYRKL modulator5Escherichia coliMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 4.16 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.219 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 217.148α = 90
b = 123.518β = 118
c = 140.558γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data scaling
PDB_EXTRACTdata extraction
HKL-2000data reduction
MOLREPphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2020-09-02
    Type: Initial release
  • Version 1.1: 2020-10-14
    Changes: Database references
  • Version 1.2: 2023-11-22
    Changes: Data collection, Database references, Refinement description