5RXA

INPP5D PanDDA analysis group deposition -- Crystal Structure of the phosphatase and C2 domains of SHIP1 in complex with Z2856434829


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.24 Å
  • R-Value Free: 0.187 
  • R-Value Work: 0.169 
  • R-Value Observed: 0.170 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Regulation of inositol 5-phosphatase activity by the C2 domain of SHIP1 and SHIP2.

Bradshaw, W.J.Kennedy, E.C.Moreira, T.Smith, L.A.Chalk, R.Katis, V.L.Benesch, J.L.P.Brennan, P.E.Murphy, E.J.Gileadi, O.

(2024) Structure 

  • DOI: https://doi.org/10.1016/j.str.2024.01.005
  • Primary Citation of Related Structures:  
    5RW2, 5RW3, 5RW4, 5RW5, 5RW6, 5RW7, 5RW8, 5RW9, 5RWA, 5RWB, 5RWC, 5RWD, 5RWE, 5RWF, 5RWG, 5RWH, 5RWI, 5RWJ, 5RWK, 5RWL, 5RWM, 5RWN, 5RWO, 5RWP, 5RWQ, 5RWR, 5RWS, 5RWT, 5RWU, 5RWV, 5RWW, 5RWX, 5RWY, 5RWZ, 5RX0, 5RX1, 5RX2, 5RX3, 5RX4, 5RX5, 5RX6, 5RX7, 5RX8, 5RX9, 5RXA, 5RXB, 5RXC, 5RXD, 5RXE, 5RXF

  • PubMed Abstract: 

    SHIP1, an inositol 5-phosphatase, plays a central role in cellular signaling. As such, it has been implicated in many conditions. Exploiting SHIP1 as a drug target will require structural knowledge and the design of selective small molecules. We have determined apo, and magnesium and phosphate-bound structures of the phosphatase and C2 domains of SHIP1. The C2 domains of SHIP1 and the related SHIP2 modulate the activity of the phosphatase domain. To understand the mechanism, we performed activity assays, hydrogen-deuterium exchange mass spectrometry, and molecular dynamics on SHIP1 and SHIP2. Our findings demonstrate that the influence of the C2 domain is more pronounced for SHIP2 than SHIP1. We determined 91 structures of SHIP1 with fragments bound, with some near the interface between the two domains. We performed a mass spectrometry screen and determined four structures with covalent fragments. These structures could act as starting points for the development of potent, selective probes.


  • Organizational Affiliation

    ARUK Oxford Drug Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine Research Building, Old Road Campus, University of Oxford, Oxford OX3 7FZ, UK. Electronic address: [email protected].


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1463Homo sapiensMutation(s): 0 
Gene Names: INPP5DSHIPSHIP1
EC: 3.1.3.86 (PDB Primary Data), 3.1.3.56 (PDB Primary Data), 3.1.3.36 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for Q92835 (Homo sapiens)
Explore Q92835 
Go to UniProtKB:  Q92835
PHAROS:  Q92835
GTEx:  ENSG00000168918 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ92835
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.24 Å
  • R-Value Free: 0.187 
  • R-Value Work: 0.169 
  • R-Value Observed: 0.170 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 62.55α = 90
b = 79.42β = 90
c = 89.49γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
Aimlessdata scaling
PDB_EXTRACTdata extraction
XDSdata reduction
REFMACphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2020-11-11
    Type: Initial release
  • Version 1.1: 2024-02-14
    Changes: Data collection, Database references