Evidence map›Paper›PMID 38309262›Full record

ArticleStructure (London, England : 1993)2024

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

William J Bradshaw, Emma C Kennedy, Tiago Moreira, Luke A Smith, Rod Chalk, Vittorio L Katis, Justin L P Benesch, Paul E Brennan, Emma J Murphy, Opher Gileadi

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Structure (London, England : 1993), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
5.1field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 22 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

William J BradshawARUK 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: william.bradshaw@cmd.ox.ac.uk.
Emma C KennedyARUK Oxford Drug Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine Research Building, Old Road Campus, University of Oxford, Oxford OX3 7FZ, UK.
Tiago MoreiraARUK Oxford Drug Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine Research Building, Old Road Campus, University of Oxford, Oxford OX3 7FZ, UK.
Luke A SmithKavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Rod ChalkARUK Oxford Drug Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine Research Building, Old Road Campus, University of Oxford, Oxford OX3 7FZ, UK.
Vittorio L KatisARUK Oxford Drug Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine Research Building, Old Road Campus, University of Oxford, Oxford OX3 7FZ, UK.
Justin L P BeneschKavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Paul E BrennanARUK Oxford Drug Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine Research Building, Old Road Campus, University of Oxford, Oxford OX3 7FZ, UK.
Emma J MurphyARUK Oxford Drug Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine Research Building, Old Road Campus, University of Oxford, Oxford OX3 7FZ, UK.
Opher GileadiARUK 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: opher.gileadi@ki.se.
University of Oxford · GB

Funding

TREAT AD Structural Biology CoreU54AG065187 · NIA · EMORY UNIVERSITY · PI Gregory W Carter, ALLAN I LEVEY · 2019 to 2026
$69.7M
NIA NIH HHS U54 AG065187
6 · The paper itself

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.

Indexed as

C2 DomainsPhosphoric Monoester HydrolasesHumansInositol Polyphosphate 5-PhosphatasesPhosphatidylinositol-3,4,5-Trisphosphate 5-PhosphatasesInositol Polyphosphate 5-PhosphatasesINPP5D protein, humanINPPL1 protein, humanPhosphatidylinositol-3,4,5-Trisphosphate 5-PhosphatasesPhosphoric Monoester HydrolasesallosteryAlzheimer'sfragment screenHDXINPP5SHIP1SHIP2XChem

Identifiers

PMID38309262
PMCPMC10997489
OpenAlexW4391470364

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.