RCSB PDB - 5R88: PanDDA analysis group deposition INTERLEUKIN-1 BETA -- Fragment Z1545313172 in complex with INTERLEUKIN-1 BETA

 5R88

PanDDA analysis group deposition INTERLEUKIN-1 BETA -- Fragment Z1545313172 in complex with INTERLEUKIN-1 BETA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.48 Å
  • R-Value Free: 0.223 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.197 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Mining the PDB for Tractable Cases Where X-ray Crystallography Combined with Fragment Screens Can Be Used to Systematically Design Protein-Protein Inhibitors: Two Test Cases Illustrated by IL1 beta-IL1R and p38 alpha-TAB1 Complexes.

Nichols, C.Ng, J.Keshu, A.Kelly, G.Conte, M.R.Marber, M.S.Fraternali, F.De Nicola, G.F.

(2020) J Med Chem 63: 7559-7568

  • DOI: https://doi.org/10.1021/acs.jmedchem.0c00403
  • Primary Citation of Related Structures:  
    5R85, 5R86, 5R87, 5R88, 5R89, 5R8A, 5R8B, 5R8C, 5R8D, 5R8E, 5R8F, 5R8G, 5R8H, 5R8I, 5R8J, 5R8K, 5R8L, 5R8M, 5R8N, 5R8O, 5R8P, 5R8Q, 5R8U, 5R8V, 5R8W, 5R8X, 5R8Y, 5R8Z, 5R90, 5R91, 5R92, 5R93, 5R94, 5R95, 5R96, 5R97, 5R98, 5R99, 5R9A, 5R9B, 5R9C, 5R9D, 5R9E, 5R9F, 5R9G, 5R9H, 5R9I, 5R9J, 5R9K, 5R9L

  • PubMed Abstract: 

    Nowadays, it is possible to combine X-ray crystallography and fragment screening in a medium throughput fashion to chemically probe the surfaces used by proteins to interact and use the outcome of the screens to systematically design protein-protein inhibitors. To prove it, we first performed a bioinformatics analysis of the Protein Data Bank protein complexes, which revealed over 400 cases where the crystal lattice of the target in the free form is such that large portions of the interacting surfaces are free from lattice contacts and therefore accessible to fragments during soaks. Among the tractable complexes identified, we then performed single fragment crystal screens on two particular interesting cases: the Il1β-ILR and p38α-TAB1 complexes. The result of the screens showed that fragments tend to bind in clusters, highlighting the small-molecule hotspots on the surface of the target protein. In most of the cases, the hotspots overlapped with the binding sites of the interacting proteins.


  • Organizational Affiliation

    British Heart Foundation Centre of Excellence, Department of Cardiology, The Rayne Institute, St Thomas' Hospital, King's College London, London SE1 7EH, U.K.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Interleukin-1 beta153Homo sapiensMutation(s): 0 
Gene Names: IL1BIL1F2
UniProt & NIH Common Fund Data Resources
Find proteins for P01584 (Homo sapiens)
Explore P01584 
Go to UniProtKB:  P01584
PHAROS:  P01584
GTEx:  ENSG00000125538 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01584
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.48 Å
  • R-Value Free: 0.223 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.197 
  • Space Group: P 43
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 54.52α = 90
b = 54.52β = 90
c = 75.36γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
Aimlessdata scaling
PDB_EXTRACTdata extraction
XDSdata reduction
REFMACphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2020-04-22
    Type: Initial release
  • Version 1.1: 2020-07-22
    Changes: Database references
  • Version 1.2: 2020-08-05
    Changes: Database references
  • Version 1.3: 2024-03-06
    Changes: Data collection, Database references