3PP1 | pdb_00003pp1

Crystal Structure of the Human Mitogen-activated protein kinase kinase 1 (MEK 1) in complex with ligand and MgATP

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 
    0.219 (Depositor), 0.230 (DCC) 
  • R-Value Work: 
    0.182 (Depositor), 0.180 (DCC) 
  • R-Value Observed: 
    0.184 (Depositor) 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted ATPClick on this verticalbar to view detailsBest fitted IZGClick on this verticalbar to view details

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


Literature

Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer.

Dong, Q., Dougan, D.R., Gong, X., Halkowycz, P., Jin, B., Kanouni, T., O'Connell, S.M., Scorah, N., Shi, L., Wallace, M.B., Zhou, F.

(2011) Bioorg Med Chem Lett 21: 1315-1319

  • DOI: https://doi.org/10.1016/j.bmcl.2011.01.071
  • Primary Citation of Related Structures:  
    3PP1

  • PubMed Abstract: 

    A novel 5-phenylamino-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione series of MEK inhibitors has been developed using structure-based drug design. Lead optimization of this series led to the discovery of TAK-733. This was advanced to Phase I clinical studies for cancer treatment.

    • Organizational Affiliation: 

    Takeda San Diego, San Diego, CA 92121, USA.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Dual specificity mitogen-activated protein kinase kinase 1328Homo sapiensMutation(s): 0 
Gene Names: MAP2K1, Mapk/erk kinase 1, MEK1, PRKMK1
EC: 2.7.12.2
UniProt & NIH Common Fund Data Resources
Find proteins for Q02750 (Homo sapiens)
Explore Q02750 
Go to UniProtKB:  Q02750
PHAROS:  Q02750
GTEx:  ENSG00000169032 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ02750
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
IZG BindingDB:  3PP1 IC50: min: 1.8, max: 6.9 (nM) from 4 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free:  0.219 (Depositor), 0.230 (DCC) 
  • R-Value Work:  0.182 (Depositor), 0.180 (DCC) 
  • R-Value Observed: 0.184 (Depositor) 
Space Group: P 62
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 82.086α = 90
b = 82.086β = 90
c = 129.254γ = 120
Software Package:
Software NamePurpose
Blu-Icedata collection
MOLREPphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted ATPClick on this verticalbar to view detailsBest fitted IZGClick on this verticalbar to view details

View more in-depth experimental data
Entry History 

Deposition Data

  • Released Date: 2011-02-23 
    • Deposition Author(s): Dougan, D.R.

Revision History  (Full details and data files)

  • Version 1.0: 2011-02-23
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-08
    Changes: Refinement description
  • Version 1.3: 2024-02-21
    Changes: Data collection, Database references, Derived calculations