3HHA

Crystal structure of cathepsin L in complex with AZ12878478


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.27 Å
  • R-Value Free: 0.152 
  • R-Value Work: 0.116 
  • R-Value Observed: 0.118 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Dipeptidyl nitrile inhibitors of Cathepsin L.

Asaad, N.Bethel, P.A.Coulson, M.D.Dawson, J.E.Ford, S.J.Gerhardt, S.Grist, M.Hamlin, G.A.James, M.J.Jones, E.V.Karoutchi, G.I.Kenny, P.W.Morley, A.D.Oldham, K.Rankine, N.Ryan, D.Wells, S.L.Wood, L.Augustin, M.Krapp, S.Simader, H.Steinbacher, S.

(2009) Bioorg Med Chem Lett 19: 4280-4283

  • DOI: https://doi.org/10.1016/j.bmcl.2009.05.071
  • Primary Citation of Related Structures:  
    3HHA

  • PubMed Abstract: 

    A series of potent Cathepsin L inhibitors with good selectivity with respect to other cysteine Cathepsins is described and SAR is discussed with reference to the crystal structure of a protein-ligand complex.


  • Organizational Affiliation

    Respiratory & Inflammation Research Area, AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cathepsin L1
A, B, C, D
220Homo sapiensMutation(s): 1 
Gene Names: CTSL1CTSL
EC: 3.4.22.15
UniProt & NIH Common Fund Data Resources
Find proteins for P07711 (Homo sapiens)
Explore P07711 
Go to UniProtKB:  P07711
PHAROS:  P07711
GTEx:  ENSG00000135047 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP07711
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NOW
Query on NOW

Download Ideal Coordinates CCD File 
E [auth A],
H [auth B],
J [auth C],
K [auth D]
Nalpha-[(3-tert-butyl-1-methyl-1H-pyrazol-5-yl)carbonyl]-N-[(2Z)-2-iminoethyl]-3-methyl-L-phenylalaninamide
C21 H29 N5 O2
TVOGNNSPACVESK-QPCOYWRUSA-N
PG4
Query on PG4

Download Ideal Coordinates CCD File 
F [auth A]TETRAETHYLENE GLYCOL
C8 H18 O5
UWHCKJMYHZGTIT-UHFFFAOYSA-N
PGE
Query on PGE

Download Ideal Coordinates CCD File 
I [auth B]TRIETHYLENE GLYCOL
C6 H14 O4
ZIBGPFATKBEMQZ-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
L [auth D]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ACT
Query on ACT

Download Ideal Coordinates CCD File 
G [auth A]ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
NOW PDBBind:  3HHA IC50: 12.6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.27 Å
  • R-Value Free: 0.152 
  • R-Value Work: 0.116 
  • R-Value Observed: 0.118 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.26α = 105.6
b = 62.69β = 93.22
c = 68.24γ = 115.55
Software Package:
Software NamePurpose
XDLdata collection
MOLREPphasing
REFMACrefinement
XDSdata reduction
XSCALEdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2009-06-23
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.2: 2018-05-30
    Changes: Advisory, Data collection, Derived calculations
  • Version 1.3: 2021-10-13
    Changes: Database references, Derived calculations