8BK3 | pdb_00008bk3

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

PDB DOI: https://doi.org/10.2210/pdb8BK3/pdb

Classification: ANTIMICROBIAL PROTEIN
Organism(s): Mycobacterium tuberculosis
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2022-11-08 Released: 2023-11-22
Deposition Author(s): de Munnik, M., Schofield, C.J.
Funding Organization(s): Biotechnology and Biological Sciences Research Council (BBSRC)

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

This is version 1.1 of the entry. See complete history.

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

PubMed: 37815791 Search on PubMedSearch on PubMed Central
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.

Macromolecule Content

Total Structure Weight: 76.74 kDa
Atom Count: 6,129
Modelled Residue Count: 703
Deposited Residue Count: 710
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
L,D-transpeptidase 2	A, B	355	Mycobacterium tuberculosis	Mutation(s): 0 Gene Names: ldtB, MT2594, V735_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 Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	I6Y9J2
Sequence Annotations Expand
Reference Sequence LOADING

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
QXU (Subject of Investigation/LOI) Query on QXU Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A] mmCIF format, chain C [auth A]	C [auth A]	1-[(2~{S},3~{R})-3-phenyloxiran-2-yl]ethanone C₁₀ H₁₀ O₂ IGCQIHCZUYCYAA-NXEZZACHSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain G [auth A] MOL2 format, chain G [auth A] mmCIF format, chain G [auth A]	G [auth A]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain G [auth A] Interactions & Density Focus chain G [auth A]
DMS Query on DMS Download Ideal Coordinates CCD File SDF format, chain J [auth B] SDF format, chain K [auth B] MOL2 format, chain J [auth B] MOL2 format, chain K [auth B] mmCIF format, chain J [auth B] mmCIF format, chain K [auth B]	J [auth B], K [auth B]	DIMETHYL SULFOXIDE C₂ H₆ O S IAZDPXIOMUYVGZ-UHFFFAOYSA-N		Interactions Focus chain J [auth B] Focus chain K [auth B] Interactions & Density Focus chain J [auth B] Focus chain K [auth B]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain H [auth A] MOL2 format, chain H [auth A] mmCIF format, chain H [auth A]	H [auth A]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain H [auth A] Interactions & Density Focus chain H [auth A]
NO3 Query on NO3 Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain I [auth B] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain I [auth B] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain F [auth A] mmCIF format, chain I [auth B]	D [auth A], E [auth A], F [auth A], I [auth B]	NITRATE ION N O₃ NHNBFGGVMKEFGY-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain I [auth B] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain I [auth B]