4UMP

Structure of MELK in complex with inhibitors

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.291 
  • R-Value Work: 0.235 
  • R-Value Observed: 0.238 

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


Literature

Fragment-Based Discovery of Type I Inhibitors of Maternal Embryonic Leucine Zipper Kinase

Johnson, C.N., Berdini, V., Beke, L., Bonnet, P., Brehmer, D., Coyle, J.E., Day, P.J., Frederickson, M., Freyne, E.J.E., Gilissen, R.A.H.J., Hamlett, C.C.F., Howard, S., Meerpoel, L., Mcmenamin, R., Patel, S., Rees, D.C., Sharff, A., Sommen, F., Wu, T., Linders, J.T.M.

(2015) ACS Med Chem Lett 6: 25

  • DOI: https://doi.org/10.1021/ml5001245
  • Primary Citation of Related Structures:  
    4D2P, 4D2T, 4D2V, 4D2W, 4UMP, 4UMQ, 4UMR

  • PubMed Abstract: 

    Fragment-based drug design was successfully applied to maternal embryonic leucine zipper kinase (MELK). A low affinity (160 μM) fragment hit was identified, which bound to the hinge region with an atypical binding mode, and this was optimized using structure-based design into a low-nanomolar and cell-penetrant inhibitor, with a good selectivity profile, suitable for use as a chemical probe for elucidation of MELK biology.

    • Organizational Affiliation: 

    Astex Pharmaceuticals , 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, United Kingdom.


Macromolecules
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(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE
A, B, C, D
356Homo sapiensMutation(s): 7 
EC: 2.7.11.1 (PDB Primary Data), 2.7.10.2 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for Q14680 (Homo sapiens)
Explore Q14680 
Go to UniProtKB:  Q14680
PHAROS:  Q14680
GTEx:  ENSG00000165304 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ14680
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.291 
  • R-Value Work: 0.235 
  • R-Value Observed: 0.238 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.822α = 86.47
b = 74.968β = 70.06
c = 77.088γ = 89.94
Software Package:
Software NamePurpose
BUSTERrefinement
d*TREKdata reduction
d*TREKdata scaling

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: 2014-10-08
    Type: Initial release
  • Version 1.1: 2015-01-28
    Changes: Database references
  • Version 1.2: 2018-04-04
    Changes: Data collection
  • Version 1.3: 2024-05-08
    Changes: Data collection, Database references, Derived calculations, Other