4MUG

Crystal structure of pantothenate synthetase in complex with 2-(5-methoxy-2-(morpholinosulfonylcarbamoyl)-1H-indol-1-yl)acetic acid


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.54 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.197 

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Ligand Structure Quality Assessment 


This is version 1.2 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
300Mycobacterium tuberculosisMutation(s): 2 
Gene Names: MT3707MTCY07H7B.20panCRv3602c
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 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
2DK
Query on 2DK

Download Ideal Coordinates CCD File 
G [auth A],
K [auth B]
{5-methoxy-2-[(morpholin-4-ylsulfonyl)carbamoyl]-1H-indol-1-yl}acetic acid
C16 H19 N3 O7 S
BNCOTZAAIISTRX-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
H [auth A],
J [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
EDO
Query on EDO

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

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.54 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.197 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.27α = 90
b = 70.88β = 99.11
c = 81.59γ = 90
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

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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: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description