6D2S

Mycobacterium tuberculosis transcriptional regulator


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.82 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.178 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural and functional insight into the Mycobacterium tuberculosis protein PrpR reveals a novel type of transcription factor.

Tang, S.Hicks, N.D.Cheng, Y.S.Silva, A.Fortune, S.M.Sacchettini, J.C.

(2019) Nucleic Acids Res 47: 9934-9949

  • DOI: https://doi.org/10.1093/nar/gkz724
  • Primary Citation of Related Structures:  
    6CYJ, 6CYY, 6CZ6, 6D2S

  • PubMed Abstract: 

    The pathogenicity of Mycobacterium tuberculosis depends upon its ability to catabolize host cholesterol. Upregulation of the methylcitrate cycle (MCC) is required to assimilate and detoxify propionyl-CoA, a cholesterol degradation product. The transcription of key genes prpC and prpD in MCC is activated by MtPrpR, a member of a family of prokaryotic transcription factors whose structures and modes of action have not been clearly defined. We show that MtPrpR has a novel overall structure and directly binds to CoA or short-chain acyl-CoA derivatives to form a homotetramer that covers the binding cavity and locks CoA tightly inside the protein. The regulation of this process involves a [4Fe4S] cluster located close to the CoA-binding cavity on a neighboring chain. Mutations in the [4Fe4S] cluster binding residues rendered MtPrpR incapable of regulating MCC gene transcription. The structure of MtPrpR without the [4Fe4S] cluster-binding region shows a conformational change that prohibits CoA binding. The stability of this cluster means it is unlikely a redox sensor but may function by sensing ambient iron levels. These results provide mechanistic insights into this family of critical transcription factors who share similar structures and regulate gene transcription using a combination of acyl-CoAs and [4Fe4S] cluster.


  • Organizational Affiliation

    Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77840, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HTH-type transcriptional regulator PrpR289Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: prpRRv1129cRVBD_1129cP425_01178
UniProt
Find proteins for O06581 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore O06581 
Go to UniProtKB:  O06581
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO06581
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EDO
Query on EDO

Download Ideal Coordinates CCD File 
H [auth A]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
B [auth A],
C [auth A]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
NA
Query on NA

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.82 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.178 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 74.999α = 90
b = 81.724β = 90
c = 95.365γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
SCALEPACKdata scaling
PDB_EXTRACTdata extraction
HKL-2000data reduction
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2019-04-17
    Type: Initial release
  • Version 1.1: 2019-10-30
    Changes: Data collection, Database references
  • Version 1.2: 2023-10-04
    Changes: Data collection, Database references, Derived calculations, Refinement description