3BWK

Crystal Structure of Falcipain-3 with Its inhibitor, K11017


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.42 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.176 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Vinyl sulfones as antiparasitic agents and a structural basis for drug design.

Kerr, I.D.Lee, J.H.Farady, C.J.Marion, R.Rickert, M.Sajid, M.Pandey, K.C.Caffrey, C.R.Legac, J.Hansell, E.McKerrow, J.H.Craik, C.S.Rosenthal, P.J.Brinen, L.S.

(2009) J Biol Chem 284: 25697-25703

  • DOI: https://doi.org/10.1074/jbc.M109.014340
  • Primary Citation of Related Structures:  
    2OZ2, 2P7U, 3BWK

  • PubMed Abstract: 

    Cysteine proteases of the papain superfamily are implicated in a number of cellular processes and are important virulence factors in the pathogenesis of parasitic disease. These enzymes have therefore emerged as promising targets for antiparasitic drugs. We report the crystal structures of three major parasite cysteine proteases, cruzain, falcipain-3, and the first reported structure of rhodesain, in complex with a class of potent, small molecule, cysteine protease inhibitors, the vinyl sulfones. These data, in conjunction with comparative inhibition kinetics, provide insight into the molecular mechanisms that drive cysteine protease inhibition by vinyl sulfones, the binding specificity of these important proteases and the potential of vinyl sulfones as antiparasitic drugs.


  • Organizational Affiliation

    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158-2550, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cysteine protease falcipain-3
A, B, C, D
243Plasmodium falciparumMutation(s): 0 
EC: 3.4.22
UniProt
Find proteins for Q8IIL0 (Plasmodium falciparum (isolate 3D7))
Explore Q8IIL0 
Go to UniProtKB:  Q8IIL0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8IIL0
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
C1P
Query on C1P

Download Ideal Coordinates CCD File 
E [auth A],
G [auth B],
J [auth C],
L [auth D]
N~2~-(morpholin-4-ylcarbonyl)-N-[(3S)-1-phenyl-5-(phenylsulfonyl)pentan-3-yl]-L-leucinamide
C28 H39 N3 O5 S
IHIAYQGDASIWGA-AHWVRZQESA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
F [auth A],
H [auth B],
I [auth B],
K [auth C],
M [auth D]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Binding Affinity Annotations 
IDSourceBinding Affinity
C1P PDBBind:  3BWK Kd: 1.14e+5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.42 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.176 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 113.996α = 90
b = 113.996β = 90
c = 226.116γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
ADSCdata collection
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-01-20
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2011-09-07
    Changes: Non-polymer description
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description