4XH6

Crystal structure of proto-oncogene kinase Pim1 bound to hispidulin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.04 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Total Synthesis of Hispidulin and the Structural Basis for Its Inhibition of Proto-oncogene Kinase Pim-1

Chao, S.-W.Su, M.-Y.Chiou, L.-C.Chen, L.-C.Chang, C.-I.Huang, W.-J.

(2015) J Nat Prod 78: 1969-1976

  • DOI: https://doi.org/10.1021/acs.jnatprod.5b00324
  • Primary Citation of Related Structures:  
    4XH6

  • PubMed Abstract: 

    A new method is applied to synthesize hispidulin, a natural flavone with a broad spectrum of biological activities. Hispidulin exhibits inhibitory activity against the oncogenic protein kinase Pim-1. Crystallographic analysis of Pim-1 bound to hispidulin reveals a binding mode distinct from that of quercetin, suggesting that the binding potency of flavonoids is determined by their hydrogen-bonding interactions with the hinge region of the kinase. Overall, this work may facilitate construction of a library of hispidulin-derived compounds for investigating the structure-activity relationship of flavone-based Pim-1 inhibitors.


  • Organizational Affiliation

    Institute of Biological Chemistry, Academia Sinica , Taipei 115, Taiwan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serine/threonine-protein kinase pim-1294Homo 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
HUL
Query on HUL

Download Ideal Coordinates CCD File 
B [auth A]5,7-dihydroxy-2-(4-hydroxyphenyl)-6-methoxy-4H-chromen-4-one
C16 H12 O6
IHFBPDAQLQOCBX-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
HUL Binding MOAD:  4XH6 IC50: 2710 (nM) from 1 assay(s)
BindingDB:  4XH6 IC50: 2710 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.04 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 
  • Space Group: P 65
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 97.999α = 90
b = 97.999β = 90
c = 80.599γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
Cootmodel building
HKL-2000data processing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-08-26
    Type: Initial release
  • Version 1.1: 2015-09-09
    Changes: Database references
  • Version 1.2: 2020-02-05
    Changes: Data collection, Derived calculations
  • Version 1.3: 2023-11-08
    Changes: Data collection, Database references, Refinement description