5LBY

Structure of the human quinone reductase 2 (NQO2) in complex with crenolanib


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.125 
  • R-Value Work: 0.105 
  • R-Value Observed: 0.106 

Starting Model: experimental
View more details

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

The target landscape of clinical kinase drugs.

Klaeger, S.Heinzlmeir, S.Wilhelm, M.Polzer, H.Vick, B.Koenig, P.A.Reinecke, M.Ruprecht, B.Petzoldt, S.Meng, C.Zecha, J.Reiter, K.Qiao, H.Helm, D.Koch, H.Schoof, M.Canevari, G.Casale, E.Depaolini, S.R.Feuchtinger, A.Wu, Z.Schmidt, T.Rueckert, L.Becker, W.Huenges, J.Garz, A.K.Gohlke, B.O.Zolg, D.P.Kayser, G.Vooder, T.Preissner, R.Hahne, H.Tonisson, N.Kramer, K.Gotze, K.Bassermann, F.Schlegl, J.Ehrlich, H.C.Aiche, S.Walch, A.Greif, P.A.Schneider, S.Felder, E.R.Ruland, J.Medard, G.Jeremias, I.Spiekermann, K.Kuster, B.

(2017) Science 358

  • DOI: https://doi.org/10.1126/science.aan4368
  • Primary Citation of Related Structures:  
    5LBW, 5LBY, 5LBZ, 5M5A, 5MAF, 5MAG, 5MAH, 5MAI

  • PubMed Abstract: 

    Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.


  • Organizational Affiliation

    Chair of Proteomics and Bioanalytics, Technical University of Munich (TUM), Freising, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosyldihydronicotinamide dehydrogenase [quinone]
A, B
237Homo sapiensMutation(s): 0 
Gene Names: NQO2NMOR2
EC: 1.10.5.1
UniProt & NIH Common Fund Data Resources
Find proteins for P16083 (Homo sapiens)
Explore P16083 
Go to UniProtKB:  P16083
PHAROS:  P16083
GTEx:  ENSG00000124588 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP16083
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.125 
  • R-Value Work: 0.105 
  • R-Value Observed: 0.106 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 61.586α = 90
b = 79.401β = 90
c = 106.571γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XDSdata scaling
REFMACphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
German Research FoundationGermany--

Revision History  (Full details and data files)

  • Version 1.0: 2017-11-29
    Type: Initial release
  • Version 1.1: 2017-12-06
    Changes: Database references
  • Version 1.2: 2017-12-13
    Changes: Database references
  • Version 1.3: 2024-01-10
    Changes: Data collection, Database references, Refinement description