3KKU

Cruzain in complex with a non-covalent ligand


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.28 Å
  • R-Value Free: 0.144 
  • R-Value Work: 0.115 
  • R-Value Observed: 0.116 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted B95Click on this verticalbar to view details

This is version 1.3 of the entry. See complete history


Literature

Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors.

Ferreira, R.S.Simeonov, A.Jadhav, A.Eidam, O.Mott, B.T.Keiser, M.J.McKerrow, J.H.Maloney, D.J.Irwin, J.J.Shoichet, B.K.

(2010) J Med Chem 53: 4891-4905

  • DOI: https://doi.org/10.1021/jm100488w
  • Primary Citation of Related Structures:  
    3KKU

  • PubMed Abstract: 

    Virtual and high-throughput screens (HTS) should have complementary strengths and weaknesses, but studies that prospectively and comprehensively compare them are rare. We undertook a parallel docking and HTS screen of 197861 compounds against cruzain, a thiol protease target for Chagas disease, looking for reversible, competitive inhibitors. On workup, 99% of the hits were eliminated as false positives, yielding 146 well-behaved, competitive ligands. These fell into five chemotypes: two were prioritized by scoring among the top 0.1% of the docking-ranked library, two were prioritized by behavior in the HTS and by clustering, and one chemotype was prioritized by both approaches. Determination of an inhibitor/cruzain crystal structure and comparison of the high-scoring docking hits to experiment illuminated the origins of docking false-negatives and false-positives. Prioritizing molecules that are both predicted by docking and are HTS-active yields well-behaved molecules, relatively unobscured by the false-positives to which both techniques are individually prone.


  • Organizational Affiliation

    Graduate Program in Chemistry and Chemical Biology, University of California San Francisco, California 94158, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cruzipain215Trypanosoma cruziMutation(s): 0 
EC: 3.4.22.51
UniProt
Find proteins for P25779 (Trypanosoma cruzi)
Explore P25779 
Go to UniProtKB:  P25779
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP25779
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
B95
Query on B95

Download Ideal Coordinates CCD File 
B [auth A]N-[2-(1H-benzimidazol-2-yl)ethyl]-2-(2-bromophenoxy)acetamide
C17 H16 Br N3 O2
XWFRNTHGPRGCNS-UHFFFAOYSA-N
Z22
Query on Z22

Download Ideal Coordinates CCD File 
M [auth A]S-methyl methanesulfonothioate
C2 H6 O2 S2
XYONNSVDNIRXKZ-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
E [auth A]
F [auth A]
G [auth A]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
B95 PDBBind:  3KKU Ki: 2000 (nM) from 1 assay(s)
BindingDB:  3KKU Ki: 2000 (nM) from 1 assay(s)
IC50: 800 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.28 Å
  • R-Value Free: 0.144 
  • R-Value Work: 0.115 
  • R-Value Observed: 0.116 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 82.978α = 90
b = 82.978β = 90
c = 101.733γ = 120
Software Package:
Software NamePurpose
PHASERphasing
PHENIXrefinement
MOSFLMdata reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted B95Click on this verticalbar to view details

Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-07-07
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description
  • Version 1.3: 2024-11-27
    Changes: Structure summary