7W06

Itaconate inducible LysR-Type Transcriptional regulator (ITCR) in complex with itaconate (SeMet labeled), Space group C121.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.195 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.177 

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Ligand Structure Quality Assessment 


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Literature

A genetically encoded fluorescent biosensor for detecting itaconate with subcellular resolution in living macrophages.

Sun, P.Zhang, Z.Wang, B.Liu, C.Chen, C.Liu, P.Li, X.

(2022) Nat Commun 13: 6562-6562

  • DOI: https://doi.org/10.1038/s41467-022-34306-5
  • Primary Citation of Related Structures:  
    7W06, 7W07, 7W08

  • PubMed Abstract: 

    Itaconate is a newly discovered endogenous metabolite promoting an anti-inflammatory program during innate immune response, but the precise mechanisms underlying its effect remains poorly understood owing primarily to the limitations of available itaconate-monitoring techniques. Here, we develop and validate a genetically encoded fluorescent itaconate biosensor, BioITA, for directly monitoring itaconate dynamics in subcellular compartments of living macrophages. Utilizing BioITA, we monitor the itaconate dynamics in response to lipopolysaccharide (LPS) stimulation in the context of modulating itaconate transportation and metabolism. Moreover, we show that STING activation induces itaconate production, and injection of AAVs expressing cytosolic BioITA into mice allows directly reporting elevation of itaconate level in activated macrophages derived from LPS-injected mice. Thus, BioITA enables subcellular resolution imaging of itaconate in living macrophages.


  • Organizational Affiliation

    CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Transcriptional regulator, LysR family292Yersinia pseudotuberculosis YPIIIMutation(s): 0 
Gene Names: YPK_2265
UniProt
Find proteins for A0A0H3B558 (Yersinia pseudotuberculosis serotype O:3 (strain YPIII))
Explore A0A0H3B558 
Go to UniProtKB:  A0A0H3B558
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A0H3B558
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MSE
Query on MSE
A
L-PEPTIDE LINKINGC5 H11 N O2 SeMET
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.195 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.177 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.766α = 90
b = 52.369β = 123.14
c = 49.079γ = 90
Software Package:
Software NamePurpose
HKL-2000data scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Natural Science Foundation of China (NSFC)China82073060

Revision History  (Full details and data files)

  • Version 1.0: 2022-10-26
    Type: Initial release
  • Version 1.1: 2022-11-16
    Changes: Database references