4DV8

Anthrax Lethal Factor metalloproteinase in complex with the Hydroxamic acid based small molecule PT8421

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.63 Å
  • R-Value Free: 0.204 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.179 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history. 


Literature

Antidotes to anthrax lethal factor intoxication. Part 3: Evaluation of core structures and further modifications to the C2-side chain.

Jiao, G.S., Kim, S., Moayeri, M., Crown, D., Thai, A., Cregar-Hernandez, L., McKasson, L., Sankaran, B., Lehrer, A., Wong, T., Johns, L., Margosiak, S.A., Leppla, S.H., Johnson, A.T.

(2012) Bioorg Med Chem Lett 22: 2242

  • DOI: https://doi.org/10.1016/j.bmcl.2012.01.095
  • Primary Citation of Related Structures:  
    4DV8

  • PubMed Abstract: 

    Four core structures capable of providing sub-nanomolar inhibitors of anthrax lethal factor (LF) were evaluated by comparing the potential for toxicity, physicochemical properties, in vitro ADME profiles, and relative efficacy in a rat lethal toxin (LT) model of LF intoxication. Poor efficacy in the rat LT model exhibited by the phenoxyacetic acid series (3) correlated with low rat microsome and plasma stability. Specific molecular interactions contributing to the high affinity of inhibitors with a secondary amine in the C2-side chain were revealed by X-ray crystallography.

    • Organizational Affiliation: 

    PanThera Biopharma, LLC, Aiea, HI 96701, USA.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Lethal factor526Bacillus anthracisMutation(s): 0 
Gene Names: lef, pXO1-107, BXA0172, GBAA_pXO1_0172
EC: 3.4.24.83
UniProt
Find proteins for P15917 (Bacillus anthracis)
Explore P15917 
Go to UniProtKB:  P15917
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP15917
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
0LX
Query on 0LX
Download Ideal Coordinates CCD File 
C [auth A](2S)-6-[(4-fluorobenzyl)amino]-2-[(2R)-2-(4-fluorophenyl)-2-methoxyethyl]-N-hydroxyhexanamide
C22 H28 F2 N2 O3
SZPWYHRMRFNOHH-GHTZIAJQSA-N
MLI
Query on MLI
Download Ideal Coordinates CCD File 
D [auth A]MALONATE ION
C3 H2 O4
OFOBLEOULBTSOW-UHFFFAOYSA-L
ZN
Query on ZN
Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
0LX PDBBind:  4DV8 Ki: 0.58 (nM) from 1 assay(s)
BindingDB:  4DV8 Ki: 0.58 (nM) from 1 assay(s)
Binding MOAD:  4DV8 Ki: 0.58 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.63 Å
  • R-Value Free: 0.204 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.179 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.09α = 90
b = 74.253β = 90
c = 139.53γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-03-14
    Type: Initial release
  • Version 1.1: 2017-11-15
    Changes: Advisory, Refinement description
  • Version 1.2: 2024-02-28
    Changes: Advisory, Data collection, Database references, Derived calculations