3BGP

Human Pim-1 complexed with a benzoisoxazole inhibitor VX1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.213 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Docking study yields four novel inhibitors of the protooncogene pim-1 kinase.

Pierce, A.C.Jacobs, M.Stuver-Moody, C.

(2008) J Med Chem 51: 1972-1975

  • DOI: https://doi.org/10.1021/jm701248t
  • Primary Citation of Related Structures:  
    3BGP, 3BGQ, 3BGZ

  • PubMed Abstract: 

    To supplement the hits from a high throughput screen, docking was performed against Pim-1 kinase. Glide docking was augmented with a filter to require traditional or aromatic CH..O hydrogen bonds to the kinase hinge. Four diverse actives, of 96 molecules assayed, had K(i) values between 0.091 and 4.5 microM. This gives a 14-fold enrichment over the earlier HTS run, and the two crystal structures solved confirmed the binding modes predicted by docking.


  • Organizational Affiliation

    Vertex Pharmaceuticals Incorporated, 130 Waverly Street, Cambridge, MA 02139, USA. al_pierce@vrtx.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Proto-oncogene serine/threonine-protein kinase Pim-1333Homo sapiensMutation(s): 0 
Gene Names: PIM1
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for P11309 (Homo sapiens)
Explore P11309 
Go to UniProtKB:  P11309
PHAROS:  P11309
GTEx:  ENSG00000137193 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP11309
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
VX1
Query on VX1

Download Ideal Coordinates CCD File 
B [auth A]4-[3-(4-chlorophenyl)-2,1-benzisoxazol-5-yl]pyrimidin-2-amine
C17 H11 Cl N4 O
AQVFETGXIRKVAQ-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
SEP
Query on SEP
A
L-PEPTIDE LINKINGC3 H8 N O6 PSER
Binding Affinity Annotations 
IDSourceBinding Affinity
VX1 BindingDB:  3BGP Ki: 91 (nM) from 1 assay(s)
PDBBind:  3BGP Ki: 91 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.213 
  • Space Group: P 65
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 96.33α = 90
b = 96.33β = 90
c = 80.6γ = 120
Software Package:
Software NamePurpose
d*TREKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
CrystalCleardata collection
d*TREKdata reduction
CNXrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2007-12-11 
  • Deposition Author(s): Jacobs, M.D.

Revision History  (Full details and data files)

  • Version 1.0: 2007-12-11
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance