6XPP

Crystal structure of itaconate modified Mycobaterium tuberculosis isocitrate lyase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.55 Å
  • R-Value Free: 0.179 
  • R-Value Work: 0.158 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Itaconate is a covalent inhibitor of the Mycobacterium tuberculosis isocitrate lyase.

Kwai, B.X.C.Collins, A.J.Middleditch, M.J.Sperry, J.Bashiri, G.Leung, I.K.H.

(2021) RSC Med Chem 12: 57-61

  • DOI: https://doi.org/10.1039/d0md00301h
  • Primary Citation of Related Structures:  
    6XPP

  • PubMed Abstract: 

    Itaconate is a mammalian antimicrobial metabolite that inhibits the isocitrate lyases (ICLs) of Mycobacterium tuberculosis . Herein, we report that ICLs form a covalent adduct with itaconate through their catalytic cysteine residue. These results reveal atomic details of itaconate inhibition and provide insights into the catalytic mechanism of ICLs.


  • Organizational Affiliation

    School of Chemical Sciences, The University of Auckland Private Bag 92019, Victoria Street West Auckland 1142 New Zealand j.sperry@auckland.ac.nz i.leung@auckland.ac.nz.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Isocitrate lyase
A, B, C, D
428Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: iclRv0467MTV038.11
EC: 4.1.3.1
UniProt
Find proteins for P9WKK7 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WKK7 
Go to UniProtKB:  P9WKK7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WKK7
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ITN (Subject of Investigation/LOI)
Query on ITN

Download Ideal Coordinates CCD File 
E [auth A],
H [auth B],
K [auth C],
N [auth D]
2-methylidenebutanedioic acid
C5 H6 O4
LVHBHZANLOWSRM-UHFFFAOYSA-N
MG (Subject of Investigation/LOI)
Query on MG

Download Ideal Coordinates CCD File 
F [auth A]
G [auth A]
I [auth B]
J [auth B]
L [auth C]
F [auth A],
G [auth A],
I [auth B],
J [auth B],
L [auth C],
M [auth C],
O [auth D],
P [auth D]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.55 Å
  • R-Value Free: 0.179 
  • R-Value Work: 0.158 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 79.314α = 90
b = 133.171β = 90
c = 159.318γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Other privateNew Zealand--
Health Research Council (HRC)New Zealand--

Revision History  (Full details and data files)

  • Version 1.0: 2020-10-21
    Type: Initial release
  • Version 1.1: 2021-06-09
    Changes: Database references
  • Version 1.2: 2023-10-18
    Changes: Data collection, Database references, Refinement description