6RRM

Crystal structure of LdtMt2 from Mycobacterium tuberculosis bound to Ebselen

PDB DOI: https://doi.org/10.2210/pdb6RRM/pdb

Classification: ANTIMICROBIAL PROTEIN
Organism(s): Mycobacterium tuberculosis CDC1551
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2019-05-20 Released: 2019-08-14
Deposition Author(s): Brem, J., Lohans, C., Schofield, C.
Funding Organization(s): Medical Research Council (United Kingdom)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.64 Å
R-Value Free: 0.223
R-Value Work: 0.200
R-Value Observed: 0.201

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.5 of the entry. See complete history.

Literature

Targeting the Mycobacterium tuberculosis transpeptidase LdtMt2with cysteine-reactive inhibitors including ebselen.

de Munnik, M., Lohans, C.T., Lang, P.A., Langley, G.W., Malla, T.R., Tumber, A., Schofield, C.J., Brem, J.

(2019) Chem Commun (Camb) 55: 10214-10217

PubMed: 31380528 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1039/c9cc04145a
Primary Citation of Related Structures:
6RLG, 6RRM

PubMed Abstract:
The l,d-transpeptidases (Ldts) are promising antibiotic targets for treating tuberculosis. We report screening of cysteine-reactive inhibitors against LdtMt2 from Mycobacterium tuberculosis. Structural studies on LdtMt2 with potent inhibitor ebselen reveal opening of the benzisoselenazolone ring by a nucleophilic cysteine, forming a complex involving extensive hydrophobic interactions with a substrate-binding loop.

Organizational Affiliation

Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, OX1 3TA, UK. [email protected] [email protected].

Macromolecule Content

Total Structure Weight: 76.85 kDa
Atom Count: 5,942
Modelled Residue Count: 702
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 CDC1551	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

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
9JT (Subject of Investigation/LOI) Query on 9JT Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain I [auth B] MOL2 format, chain F [auth A] MOL2 format, chain I [auth B] mmCIF format, chain F [auth A] mmCIF format, chain I [auth B]	F [auth A], I [auth B]	N-phenyl-2-selanylbenzamide C₁₃ H₁₁ N O Se PVPUYGNPKBMXGO-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain I [auth B] Interactions & Density Focus chain F [auth A] Focus chain I [auth B]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain D [auth A] MOL2 format, chain D [auth A] mmCIF format, chain D [auth A]	D [auth A]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Interactions & Density Focus chain D [auth A]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain G [auth B] SDF format, chain J [auth B] MOL2 format, chain G [auth B] MOL2 format, chain J [auth B] mmCIF format, chain G [auth B] mmCIF format, chain J [auth B]	G [auth B], J [auth B]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain G [auth B] Focus chain J [auth B] Interactions & Density Focus chain G [auth B] Focus chain J [auth B]
NH4 Query on NH4 Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain E [auth A] SDF format, chain H [auth B] MOL2 format, chain C [auth A] MOL2 format, chain E [auth A] MOL2 format, chain H [auth B] mmCIF format, chain C [auth A] mmCIF format, chain E [auth A] mmCIF format, chain H [auth B]	C [auth A], E [auth A], H [auth B]	AMMONIUM ION H₄ N QGZKDVFQNNGYKY-UHFFFAOYSA-O		Interactions Focus chain C [auth A] Focus chain E [auth A] Focus chain H [auth B] Interactions & Density Focus chain C [auth A] Focus chain E [auth A] Focus chain H [auth B]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.64 Å
R-Value Free: 0.223
R-Value Work: 0.200
R-Value Observed: 0.201
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 61.22	α = 90
b = 93.57	β = 93.01
c = 75.49	γ = 90

Software Package:

Software Name	Purpose
XDS	data reduction
Aimless	data scaling
PHASER	phasing
PHENIX	refinement
PDB_EXTRACT	data extraction

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History & Funding Information

Deposition Data

Released Date: 2019-08-14

Deposition Author(s):

Brem, J.

Lohans, C.

Schofield, C.

Funding Organization	Location	Grant Number
Medical Research Council (United Kingdom)	United Kingdom	--

Revision History (Full details and data files)

Version 1.0: 2019-08-14
Type: Initial release
Version 1.1: 2019-08-21
Changes: Data collection, Derived calculations
Version 1.2: 2019-09-04
Changes: Data collection, Database references
Version 1.3: 2023-04-12
Changes: Database references, Derived calculations, Structure summary
Version 1.4: 2024-02-07
Changes: Data collection, Refinement description
Version 1.5: 2024-11-06
Changes: Structure summary