1PMU

The crystal structure of JNK3 in complex with a phenantroline inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.285 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.221 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

The structure of JNK3 in complex with small molecule inhibitors: structural basis for potency and selectivity

Scapin, G.Patel, S.B.Lisnock, J.Becker, J.W.LoGrasso, P.V.

(2003) Chem Biol 10: 705-712

  • DOI: https://doi.org/10.1016/s1074-5521(03)00159-5
  • Primary Citation of Related Structures:  
    1PMN, 1PMU, 1PMV, 4Z9L

  • PubMed Abstract: 

    The c-Jun terminal kinases (JNKs) are members of the mitogen-activated protein (MAP) kinase family and regulate signal transduction in response to environmental stress. Activation of JNK3, a neuronal-specific isoform, has been associated with neurological damage, and as such, JNK3 may represent an attractive target for the treatment of neurological disorders. The MAP kinases share between 50% and 80% sequence identity. In order to obtain efficacious and safe compounds, it is necessary to address the issues of potency and selectivity. We report here four crystal structures of JNK3 in complex with three different classes of inhibitors. These structures provide a clear picture of the interactions that each class of compound made with the kinase. Knowledge of the atomic interactions involved in these diverse binding modes provides a platform for structure-guided modification of these compounds, or the de novo design of novel inhibitors that could satisfy the need for potency and selectivity.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA. giovanna_scapin@merck.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Mitogen-activated protein kinase 10364Homo sapiensMutation(s): 0 
Gene Names: MK10_HUMAN
EC: 2.7.1
UniProt & NIH Common Fund Data Resources
Find proteins for P53779 (Homo sapiens)
Explore P53779 
Go to UniProtKB:  P53779
PHAROS:  P53779
GTEx:  ENSG00000109339 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP53779
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
9HP
Query on 9HP

Download Ideal Coordinates CCD File 
C [auth A]9-(4-HYDROXYPHENYL)-2,7-PHENANTHROLINE
C18 H12 N2 O
IUSSGTWHFMSCOY-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
B [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
9HP BindingDB:  1PMU IC50: 590 (nM) from 1 assay(s)
PDBBind:  1PMU IC50: 590 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.285 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.221 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 62.401α = 90
b = 62.377β = 90
c = 98.119γ = 90
Software Package:
Software NamePurpose
X-GENdata scaling
X-GENdata reduction
CNXrefinement
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-09-09
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 1.4: 2023-08-16
    Changes: Data collection, Database references, Derived calculations, Refinement description