4NEU

X-ray structure of Receptor Interacting Protein 1 (RIP1)kinase domain with a 1-aminoisoquinoline inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.57 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.181 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Discovery of Small Molecule RIP1 Kinase Inhibitors for the Treatment of Pathologies Associated with Necroptosis.

Harris, P.A.Bandyopadhyay, D.Berger, S.B.Campobasso, N.Capriotti, C.A.Cox, J.A.Dare, L.Finger, J.N.Hoffman, S.J.Kahler, K.M.Lehr, R.Lich, J.D.Nagilla, R.Nolte, R.T.Ouellette, M.T.Pao, C.S.Schaeffer, M.C.Smallwood, A.Sun, H.H.Swift, B.A.Totoritis, R.D.Ward, P.Marquis, R.W.Bertin, J.Gough, P.J.

(2013) ACS Med Chem Lett 4: 1238-1243

  • DOI: https://doi.org/10.1021/ml400382p
  • Primary Citation of Related Structures:  
    4NEU

  • PubMed Abstract: 

    Potent inhibitors of RIP1 kinase from three distinct series, 1-aminoisoquinolines, pyrrolo[2,3-b]pyridines, and furo[2,3-d]pyrimidines, all of the type II class recognizing a DLG-out inactive conformation, were identified from screening of our in-house kinase focused sets. An exemplar from the furo[2,3-d]pyrimidine series showed a dose proportional response in protection from hypothermia in a mouse model of TNFα induced lethal shock.


  • Organizational Affiliation

    Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Receptor-interacting serine/threonine-protein kinase 1
A, B
333Homo sapiensMutation(s): 0 
Gene Names: RIPK1RIPRIP1
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for Q13546 (Homo sapiens)
Explore Q13546 
Go to UniProtKB:  Q13546
PHAROS:  Q13546
GTEx:  ENSG00000137275 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13546
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
Q1A BindingDB:  4NEU IC50: min: 10, max: 630 (nM) from 5 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.57 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.181 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 149.249α = 90
b = 149.249β = 90
c = 187.67γ = 120
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-11-20
    Type: Initial release
  • Version 1.1: 2014-07-02
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations