8BK3 | pdb_00008bk3

Crystal structure of the transpeptidase LdtMt2 from Mycobacterium tuberculosis in complex with diepoxide ketone 1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 
    0.253 (Depositor), 0.250 (DCC) 
  • R-Value Work: 
    0.216 (Depositor), 0.220 (DCC) 
  • R-Value Observed: 
    0.218 (Depositor) 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 

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Literature

alpha beta , alpha ' beta '-Diepoxyketones are mechanism-based inhibitors of nucleophilic cysteine enzymes.

de Munnik, M.Lithgow, J.Brewitz, L.Christensen, K.E.Bates, R.H.Rodriguez-Miquel, B.Schofield, C.J.

(2023) Chem Commun (Camb) 59: 12859-12862

  • DOI: https://doi.org/10.1039/d3cc02932h
  • Primary Citation of Related Structures:  
    8BK3

  • PubMed Abstract: 

    Epoxides are an established class of electrophilic alkylating agents that react with nucleophilic protein residues. We report αβ,α'β'-diepoxyketones (DEKs) as a new type of mechanism-based inhibitors of nucleophilic cysteine enzymes. Studies with the L,D-transpeptidase Ldt Mt2 from Mycobacterium tuberculosis and the main protease from SARS-CoV-2 (M pro ) reveal that following epoxide ring opening by a nucleophilic cysteine, further reactions can occur, leading to irreversible alkylation.


  • Organizational Affiliation

    Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute of Antimicrobial Research, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK. christopher.schofield@chem.ox.ac.uk.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
L,D-transpeptidase 2
A, B
355Mycobacterium tuberculosisMutation(s): 0 
Gene Names: ldtBMT2594V735_02606
EC: 2.3.2
UniProt
Find proteins for I6Y9J2 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore I6Y9J2 
Go to UniProtKB:  I6Y9J2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupI6Y9J2
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
QXU (Subject of Investigation/LOI)
Query on QXU

Download Ideal Coordinates CCD File 
C [auth A]1-[(2~{S},3~{R})-3-phenyloxiran-2-yl]ethanone
C10 H10 O2
IGCQIHCZUYCYAA-NXEZZACHSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
G [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
DMS
Query on DMS

Download Ideal Coordinates CCD File 
J [auth B],
K [auth B]
DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
H [auth A]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
NO3
Query on NO3

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
F [auth A],
I [auth B]
NITRATE ION
N O3
NHNBFGGVMKEFGY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free:  0.253 (Depositor), 0.250 (DCC) 
  • R-Value Work:  0.216 (Depositor), 0.220 (DCC) 
  • R-Value Observed: 0.218 (Depositor) 
Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 60.933α = 90
b = 95.057β = 92.6
c = 75.535γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
xia2data scaling
PHASERphasing
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted QXUClick on this verticalbar to view details

Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Biotechnology and Biological Sciences Research Council (BBSRC)United Kingdom--

Revision History  (Full details and data files)

  • Version 1.0: 2023-11-22
    Type: Initial release
  • Version 1.1: 2024-10-16
    Changes: Structure summary