5US5

Solution structure of the IreB homodimer


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the least restraint violations 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structure and Dimerization of IreB, a Negative Regulator of Cephalosporin Resistance in Enterococcus faecalis.

Hall, C.L.Lytle, B.L.Jensen, D.Hoff, J.S.Peterson, F.C.Volkman, B.F.Kristich, C.J.

(2017) J Mol Biol 429: 2324-2336

  • DOI: https://doi.org/10.1016/j.jmb.2017.05.019
  • Primary Citation of Related Structures:  
    5US5

  • PubMed Abstract: 

    Enterococcus faecalis, a leading cause of hospital-acquired infections, exhibits intrinsic resistance to most cephalosporins, which are antibiotics in the beta-lactam family that target cell-wall biosynthesis. A comprehensive understanding of the underlying genetic and biochemical mechanisms of cephalosporin resistance in E. faecalis is lacking. We previously determined that a transmembrane serine/threonine kinase (IreK) and its cognate phosphatase (IreP) reciprocally regulate cephalosporin resistance in E. faecalis, dependent on the kinase activity of IreK. Other than IreK itself, thus far the only known substrate for reversible phosphorylation by IreK and IreP is IreB, a small protein of unknown function that is well conserved in low-GC Gram-positive bacteria. We previously showed that IreB acts as a negative regulator of cephalosporin resistance in E. faecalis. However, the biochemical mechanism by which IreB modulates cephalosporin resistance remains unknown. As a next step toward an understanding of the mechanism by which IreB regulates resistance, we initiated a structure-function study on IreB. The NMR solution structure of IreB was determined, revealing that IreB adopts a unique fold and forms a dimer in vitro. Dimerization of IreB was confirmed in vivo. Substitutions at the dimer interface impaired IreB function and stability in vivo, indicating that dimerization is functionally important for the biological activity of IreB. Hence, these studies provide new insights into the structure and function of a widely conserved protein of unknown function that is an important regulator of antimicrobial resistance in E. faecalis.


  • Organizational Affiliation

    Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Center for Infectious Disease Research, Medical College of Wisconsin, Milwaukee, WI 53226, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
UPF0297 protein EF_1202
A, B
89Enterococcus faecalis V583Mutation(s): 0 
Gene Names: EF_1202
UniProt
Find proteins for Q836B3 (Enterococcus faecalis (strain ATCC 700802 / V583))
Explore Q836B3 
Go to UniProtKB:  Q836B3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ836B3
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the least restraint violations 

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesAI081692
National Institutes of Health/Office of the DirectorUnited StatesOD006447

Revision History  (Full details and data files)

  • Version 1.0: 2017-06-14
    Type: Initial release
  • Version 1.1: 2017-07-26
    Changes: Author supporting evidence, Database references
  • Version 1.2: 2019-12-11
    Changes: Author supporting evidence, Data collection
  • Version 1.3: 2023-06-14
    Changes: Database references, Other
  • Version 1.4: 2024-05-15
    Changes: Data collection, Database references