4MQ6

Pantothenate synthase in complex with 2-(5-methoxy-2-(tosylcarbamoyl)-1H-indol-1-yl)acetic acid


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.166 
  • R-Value Observed: 0.168 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Optimization of Inhibitors of Mycobacterium tuberculosis Pantothenate Synthetase Based on Group Efficiency Analysis.

Hung, A.W.Silvestre, H.L.Wen, S.George, G.P.Boland, J.Blundell, T.L.Ciulli, A.Abell, C.

(2016) ChemMedChem 11: 38-42

  • DOI: https://doi.org/10.1002/cmdc.201500414
  • Primary Citation of Related Structures:  
    4MQ6, 4MUE, 4MUF, 4MUG, 4MUH, 4MUI, 4MUJ, 4MUK, 4MUL, 4MUN

  • PubMed Abstract: 

    Ligand efficiency has proven to be a valuable concept for optimization of leads in the early stages of drug design. Taking this one step further, group efficiency (GE) evaluates the binding efficiency of each appendage of a molecule, further fine-tuning the drug design process. Here, GE analysis is used to systematically improve the potency of inhibitors of Mycobacterium tuberculosis pantothenate synthetase, an important target in tuberculosis therapy. Binding efficiencies were found to be distributed unevenly within a lead molecule derived using a fragment-based approach. Substitution of the less efficient parts of the molecule allowed systematic development of more potent compounds. This method of dissecting and analyzing different groups within a molecule offers a rational and general way of carrying out lead optimization, with potential broad application within drug discovery.


  • Organizational Affiliation

    Department of Chemistry, University of Cambridge, Lensfield Rd, Cambridge, CB2 1EW, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Pantothenate synthetase
A, B
309Mycobacterium tuberculosisMutation(s): 2 
EC: 6.3.2.1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
29W
Query on 29W

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A],
N [auth B]
(5-methoxy-2-{[(4-methylphenyl)sulfonyl]carbamoyl}-1H-indol-1-yl)acetic acid
C19 H18 N2 O6 S
YJQRXPOQBVGZLN-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
H [auth A],
O [auth B],
P [auth B],
Q [auth B]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
EOH
Query on EOH

Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
E [auth A]
I [auth A]
J [auth A]
C [auth A],
D [auth A],
E [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A],
M [auth A]
ETHANOL
C2 H6 O
LFQSCWFLJHTTHZ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.166 
  • R-Value Observed: 0.168 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.54α = 90
b = 70.9β = 99.36
c = 81.61γ = 90
Software Package:
Software NamePurpose
MAR345data collection
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-08-27
    Type: Initial release
  • Version 1.1: 2016-11-23
    Changes: Database references
  • Version 1.2: 2017-11-15
    Changes: Refinement description
  • Version 1.3: 2018-08-29
    Changes: Data collection, Source and taxonomy, Structure summary
  • Version 1.4: 2024-02-28
    Changes: Data collection, Database references, Derived calculations