2R9S

c-Jun N-terminal Kinase 3 with 3,5-Disubstituted Quinoline inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.290 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.209 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history. 


Literature

3,5-Disubstituted quinolines as novel c-Jun N-terminal kinase inhibitors.

Jiang, R., Duckett, D., Chen, W., Habel, J., Ling, Y.Y., LoGrasso, P., Kamenecka, T.M.

(2007) Bioorg Med Chem Lett 17: 6378-6382

  • DOI: https://doi.org/10.1016/j.bmcl.2007.08.054
  • Primary Citation of Related Structures:  
    2R9S

  • PubMed Abstract: 

    The structure-based design and synthesis of a novel series of c-Jun N-terminal kinase (JNK) inhibitors with selectivity against p38 is reported. The unique structure of 3,5-disubstituted quinolines (2) was developed from the previously reported 4-(2,7-phenanthrolin-9-yl)phenol (1). The X-ray crystal structure of 16a in JNK3 reveals an unexpected binding mode for this new scaffold with protein.

    • Organizational Affiliation: 

    Department of Medicinal Chemistry, Scripps Florida, 5353 Parkside Drive, RF-2, Jupiter, FL 33458, USA. rjiang@scripps.edu


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Mitogen-activated protein kinase 10
A, B
356Homo sapiensMutation(s): 3 
Gene Names: MAPK10, JNK3, JNK3A, PRKM10
EC: 2.7.11.24
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 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
255
Query on 255
Download Ideal Coordinates CCD File 
C [auth A],
Z [auth B]		N-(tert-butyl)-4-[5-(pyridin-2-ylamino)quinolin-3-yl]benzenesulfonamide
C24 H24 N4 O2 S
GJTCKUKIFXWJKG-UHFFFAOYSA-N
TFA
Query on TFA
Download Ideal Coordinates CCD File 
KA [auth B],
U [auth A]		trifluoroacetic acid
C2 H F3 O2
DTQVDTLACAAQTR-UHFFFAOYSA-N
EDO
Query on EDO
Download Ideal Coordinates CCD File 
LA [auth B]
MA [auth B]
V [auth A]
W [auth A]
X [auth A]
LA [auth B],
MA [auth B],
V [auth A],
W [auth A],
X [auth A],
Y [auth A]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
UNX
Query on UNX
Download Ideal Coordinates CCD File 
AA [auth B]
BA [auth B]
CA [auth B]
D [auth A]
DA [auth B]
AA [auth B],
BA [auth B],
CA [auth B],
D [auth A],
DA [auth B],
E [auth A],
EA [auth B],
F [auth A],
FA [auth B],
G [auth A],
GA [auth B],
H [auth A],
HA [auth B],
I [auth A],
IA [auth B],
J [auth A],
JA [auth B],
K [auth A],
L [auth A],
M [auth A],
N [auth A],
O [auth A],
P [auth A],
Q [auth A],
R [auth A],
S [auth A],
T [auth A]
UNKNOWN ATOM OR ION
X
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
OCY
Query on OCY
A, B
L-PEPTIDE LINKINGC5 H11 N O3 SCYS
Binding Affinity Annotations 
IDSourceBinding Affinity
255 PDBBind:  2R9S IC50: 150 (nM) from 1 assay(s)
Binding MOAD:  2R9S IC50: 150 (nM) from 1 assay(s)
BindingDB:  2R9S IC50: 150 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.290 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.209 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 68.318α = 90
b = 81.344β = 90
c = 123.76γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data collection
HKL-2000data reduction
PHASERphasing

Structure Validation

View Full Validation Report



View more in-depth experimental data
Entry History 

Deposition Data

  • Released Date: 2007-10-16 
    • Deposition Author(s): Habel, J.

Revision History  (Full details and data files)

  • Version 1.0: 2007-10-16
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2017-10-25
    Changes: Refinement description
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description