3VFE

Virtual Screening and X-Ray Crystallography for Human Kallikrein 6 Inhibitors with an Amidinothiophene P1 Group


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.88 Å
  • R-Value Free: 0.223 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.195 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Human kallikrein 6 inhibitors with a para-amidobenzylanmine P1 group identified through virtual screening.

Liang, G.Chen, X.Aldous, S.Pu, S.F.Mehdi, S.Powers, E.Xia, T.Wang, R.

(2012) Bioorg Med Chem Lett 22: 2450-2455

  • DOI: https://doi.org/10.1016/j.bmcl.2012.02.014
  • Primary Citation of Related Structures:  
    3VFE, 4D8N

  • PubMed Abstract: 

    A series of hK6 inhibitors with a para-amidobenzylamine P1 group and a 2-hydroxybenzamide scaffold linker was discovered through virtual screening. The X-ray structure of hK6 complexed with compound 9b was determined to a resolution of 1.68Å. The tertiary folding of the hK6 complexed with the inhibitor is conserved relative to the structure of the apo-protein, whereas the interaction between hK6 and the inhibitor is consistent with both the SAR and the in silico model used in the virtual screening.


  • Organizational Affiliation

    Molecular Innovative Therapeutics, Sanofi Pharmaceuticals, Bridgewater, NJ, USA. guyan.liang@verizon.net


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Kallikrein-6223Homo sapiensMutation(s): 3 
Gene Names: KLK6PRSS18PRSS9
EC: 3.4.21
UniProt & NIH Common Fund Data Resources
Find proteins for Q92876 (Homo sapiens)
Explore Q92876 
Go to UniProtKB:  Q92876
PHAROS:  Q92876
GTEx:  ENSG00000167755 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ92876
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
0HL
Query on 0HL

Download Ideal Coordinates CCD File 
B [auth A]4-{[(3R)-3-{[(7-methoxynaphthalen-2-yl)sulfonyl](thiophen-3-ylmethyl)amino}-2-oxopyrrolidin-1-yl]methyl}thiophene-2-carboximidamide
C26 H26 N4 O4 S3
GWOFKCKOEZWDOK-HSZRJFAPSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.88 Å
  • R-Value Free: 0.223 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.195 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 43.938α = 90
b = 47.909β = 90
c = 107.553γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
MOLREPphasing
CNXrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-11-21
    Type: Initial release
  • Version 1.1: 2017-11-15
    Changes: Refinement description
  • Version 1.2: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description