2X5O

Discovery of Novel 5-Benzylidenerhodanine- and 5-Benzylidene- thiazolidine-2,4-dione Inhibitors of MurD Ligase

PDB DOI: https://doi.org/10.2210/pdb2X5O/pdb

Classification: LIGASE
Organism(s): Escherichia coli DH5[alpha]
Expression System: Escherichia coli DH5[alpha]
Mutation(s): No

Deposited: 2010-02-10 Released: 2010-09-15
Deposition Author(s): Zidar, N., Tomasic, T., Sink, R., Rupnik, V., Kovac, A., Turk, S., Contreras-Martel, C., Dessen, A., Blanot, D., Gobec, S., Zega, A., Peterlin-Masic, L., Kikelja, D.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.46 Å
R-Value Free: 0.217
R-Value Work: 0.185
R-Value Observed: 0.187

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Discovery of novel 5-benzylidenerhodanine and 5-benzylidenethiazolidine-2,4-dione inhibitors of MurD ligase.

Zidar, N., Tomasic, T., Sink, R., Rupnik, V., Kovac, A., Turk, S., Patin, D., Blanot, D., Contreras Martel, C., Dessen, A., Muller Premru, M., Zega, A., Gobec, S., Peterlin Masic, L., Kikelj, D.

(2010) J Med Chem 53: 6584-6594

PubMed: 20804196 Search on PubMed
DOI: https://doi.org/10.1021/jm100285g
Primary Citation of Related Structures:
2WJP, 2X5O

PubMed Abstract:
We have designed, synthesized, and evaluated 5-benzylidenerhodanine- and 5-benzylidenethiazolidine-2,4-dione-based compounds as inhibitors of bacterial enzyme MurD with E. coli IC(50) in the range 45-206 μM. The high-resolution crystal structure of MurD in complex with (R,Z)-2-(3-[{4-([2,4-dioxothiazolidin-5-ylidene]methyl)phenylamino}methyl)benzamido)pentanedioic acid [(R)-32] revealed details of the binding mode of the inhibitor within the active site and provides a good foundation for structure-based design of a novel generation of MurD inhibitors.

Organizational Affiliation

Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia.

Macromolecule Content

Total Structure Weight: 48.1 kDa
Atom Count: 4,012
Modelled Residue Count: 439
Deposited Residue Count: 439
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
UDP-N-ACETYLMURAMOYLALANINE--D-GLUTAMATE LIGASE	A	439	Escherichia coli DH5[alpha]	Mutation(s): 0 EC: 6.3.2.9
UniProt
Find proteins for P14900 (Escherichia coli (strain K12)) Explore P14900 Go to UniProtKB: P14900
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P14900
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
VSV Query on VSV Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A]	B [auth A]	N-({3-[({4-[(Z)-(2,4-DIOXO-1,3-THIAZOLIDIN-5-YLIDENE)METHYL]PHENYL}AMINO)METHYL]PHENYL}CARBONYL)-D-GLUTAMIC ACID C₂₃ H₂₁ N₃ O₇ S YITBSJALJWUAQA-LVSMMTLPSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A]	D [auth A], E [auth A]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain D [auth A] Focus chain E [auth A] Interactions & Density Focus chain D [auth A] Focus chain E [auth A]
SO3 Query on SO3 Download Ideal Coordinates CCD File SDF format, chain F [auth A] MOL2 format, chain F [auth A]	F [auth A]	SULFITE ION O₃ S LSNNMFCWUKXFEE-UHFFFAOYSA-L		Interactions Focus chain F [auth A] Interactions & Density Focus chain F [auth A]
AZI Query on AZI Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A]	C [auth A]	AZIDE ION N₃ IVRMZWNICZWHMI-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain H [auth A] SDF format, chain G [auth A] SDF format, chain I [auth A] SDF format, chain J [auth A] MOL2 format, chain H [auth A] MOL2 format, chain G [auth A] MOL2 format, chain I [auth A] MOL2 format, chain J [auth A]	G [auth A], H [auth A], I [auth A], J [auth A]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Interactions & Density Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A]

Modified Residues 1 Unique
ID	Chains	Type	Formula	2D Diagram	Parent
KCX Query on KCX	A	L-PEPTIDE LINKING	C₇ H₁₄ N₂ O₄		LYS

Binding Affinity Annotations
ID	Source	Binding Affinity
VSV	PDBBind: 2X5O	IC50: 8.50e+4 (nM) from 1 assay(s)
VSV	Binding MOAD: 2X5O	IC50: 8.50e+4 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.46 Å
R-Value Free: 0.217
R-Value Work: 0.185
R-Value Observed: 0.187
Space Group: P 4₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 66.091	α = 90
b = 66.091	β = 90
c = 135.781	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
XDS	data reduction
XSCALE	data scaling
PHASER	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2010-09-15

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2010-09-15
Type: Initial release
Version 1.1: 2011-08-31
Changes: Database references, Refinement description, Version format compliance
Version 1.2: 2018-02-28
Changes: Database references, Source and taxonomy
Version 1.3: 2023-12-20
Changes: Data collection, Database references, Derived calculations, Other, Refinement description

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Help and Resources

2X5O

Discovery of Novel 5-Benzylidenerhodanine- and 5-Benzylidene- thiazolidine-2,4-dione Inhibitors of MurD Ligase

Discovery of novel 5-benzylidenerhodanine and 5-benzylidenethiazolidine-2,4-dione inhibitors of MurD ligase.

Entity ID: 1

UniProt

Entity Groups

Sequence Annotations

Expand

Experimental Data

Structure Validation

Ligand Structure Quality Assessment

Deposition Data

Revision History (Full details and data files)