1A9U

THE COMPLEX STRUCTURE OF THE MAP KINASE P38/SB203580


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.182 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural basis of inhibitor selectivity in MAP kinases.

Wang, Z.Canagarajah, B.J.Boehm, J.C.Kassisa, S.Cobb, M.H.Young, P.R.Abdel-Meguid, S.Adams, J.L.Goldsmith, E.J.

(1998) Structure 6: 1117-1128

  • DOI: https://doi.org/10.1016/s0969-2126(98)00113-0
  • Primary Citation of Related Structures:  
    1A9U, 1BL6, 1BL7, 1BMK, 3ERK, 4ERK

  • PubMed Abstract: 

    The mitogen-activated protein (MAP) kinases are important signaling molecules that participate in diverse cellular events and are potential targets for intervention in inflammation, cancer, and other diseases. The MAP kinase p38 is responsive to environmental stresses and is involved in the production of cytokines during inflammation. In contrast, the activation of the MAP kinase ERK2 (extracellular-signal-regulated kinase 2) leads to cellular differentiation or proliferation. The anti-inflammatory agent pyridinylimidazole and its analogs (SB [SmithKline Beecham] compounds) are highly potent and selective inhibitors of p38, but not of the closely-related ERK2, or other serine/threonine kinases. Although these compounds are known to bind to the ATP-binding site, the origin of the inhibitory specificity toward p38 is not clear.


  • Organizational Affiliation

    Department of Biochemistry The University of Texas Southwestern Medical Center at Dallas 5323 Harry Hines Boulevard, Dallas, TX 75235, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
MAP KINASE P38379Homo sapiensMutation(s): 0 
EC: 2.7.1
UniProt & NIH Common Fund Data Resources
Find proteins for Q16539 (Homo sapiens)
Explore Q16539 
Go to UniProtKB:  Q16539
PHAROS:  Q16539
GTEx:  ENSG00000112062 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ16539
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SB2
Query on SB2

Download Ideal Coordinates CCD File 
B [auth A]4-[5-(4-FLUORO-PHENYL)-2-(4-METHANESULFINYL-PHENYL)-3H-IMIDAZOL-4-YL]-PYRIDINE
C21 H16 F N3 O S
CDMGBJANTYXAIV-MHZLTWQESA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SB2 PDBBind:  1A9U IC50: 48 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.182 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 45.48α = 90
b = 85.03β = 90
c = 123.13γ = 90
Software Package:
Software NamePurpose
AMoREphasing
X-PLORrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1999-04-20
    Type: Initial release
  • Version 1.1: 2008-03-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-07
    Changes: Data collection, Database references, Derived calculations