5AX3

Crystal structure of ERK2 complexed with allosteric and ATP-competitive inhibitors.

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.98 Å
  • R-Value Free: 0.285 
  • R-Value Work: 0.236 
  • R-Value Observed: 0.239 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history. 


Literature

Identification of allosteric ERK2 inhibitors through in silico biased screening and competitive binding assay

Kinoshita, T., Sugiyama, H., Mori, Y., Takahashi, N., Tomonaga, A.

(2016) Bioorg Med Chem Lett 26: 955-958

  • DOI: https://doi.org/10.1016/j.bmcl.2015.12.056
  • Primary Citation of Related Structures:  
    5AX3

  • PubMed Abstract: 

    Extracellular signal-regulated kinase 2 (ERK2) is a drug target for type 2 diabetes mellitus. A peptide-type ERK2 inhibitor (PEP) was discovered in the previous study through the knowledge-based method and showed physiological effects on the db/db mice model of type 2 diabetes. Here, the crystal structure showed that PEP bound to the allosteric site without the interruption of the ATP competitive inhibitor binding to ERK2. An in silico biased-screening using the focused library rendered three compounds with inhibitory activity of IC50 <100 μM. Among them, two compounds revealed the concentration-dependent competition with PEP and could be lead compounds for antidiabetic medicine.

    • Organizational Affiliation: 

    Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan. Electronic address: [email protected].


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Mitogen-activated protein kinase 1368Homo sapiensMutation(s): 0 
Gene Names: MAPK1, ERK2, PRKM1, PRKM2
EC: 2.7.11.24
UniProt & NIH Common Fund Data Resources
Find proteins for P28482 (Homo sapiens)
Explore P28482 
Go to UniProtKB:  P28482
PHAROS:  P28482
GTEx:  ENSG00000100030 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP28482
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
allosteric and ATP-competitive inhibitor12Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P40763 (Homo sapiens)
Explore P40763 
Go to UniProtKB:  P40763
PHAROS:  P40763
GTEx:  ENSG00000168610 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP40763
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
5ID
Query on 5ID
Download Ideal Coordinates CCD File 
C [auth A](2R,3R,4S,5R)-2-(4-AMINO-5-IODO-7H-PYRROLO[2,3-D]PYRIMIDIN-7-YL)-5-(HYDROXYMETHYL)TETRAHYDROFURAN-3,4-DIOL
C11 H13 I N4 O4
WHSIXKUPQCKWBY-IOSLPCCCSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.98 Å
  • R-Value Free: 0.285 
  • R-Value Work: 0.236 
  • R-Value Observed: 0.239 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 43.835α = 90
b = 66.465β = 90
c = 116.871γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-02-10
    Type: Initial release
  • Version 1.1: 2020-02-26
    Changes: Data collection, Database references, Derived calculations
  • Version 1.2: 2023-11-08
    Changes: Data collection, Database references, Refinement description