PXD012722

PXD012722 is an original dataset announced via ProteomeXchange.

Title	Validation and invalidation of chemical probes for the human N-myristoyltransferases.
Description	On-target, cell-active chemical probes are of fundamental importance in both chemical and cell biology, whereas the application of poorly-characterised probes often leads to invalid conclusions. Human N-myristoyltransferase (NMT) has attracted increasing interest as a target in cancer and infectious diseases; here we report an in-depth comparison of five compounds widely applied as human NMT inhibitors, using a combination of quantitative whole-proteome N-myristoylation profiling, biochemical enzyme assays, cytotoxicity, in-cell protein synthesis and cell cycle assays. We find that N-myristoylation is unaffected by 2-hydroxymyristic acid (100 μM), D-NMAPPD (30 μM) or Tris-DBA palladium (10 μM), with the latter compounds causing cytotoxicity through mechanisms unrelated to NMT. In contrast, drug-like inhibitors IMP 366 and IMP 1088 delivered complete and specific inhibition of N-myristoylation in a range of cell lines at 1 μM and 100 nM, respectively. This study enables the selection of appropriate on-target probes for future studies and suggests the need for reassessment of previous studies which used off-target compounds.
HostingRepository	PRIDE
AnnounceDate	2019-11-14
AnnouncementXML	Submission_2019-11-14_03:51:58.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wouter Kallemeijn
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-15 01:30:28	ID requested
⏵ 1	2019-11-14 03:52:00	announced

Kallemeijn WW, Lueg GA, Faronato M, Hadavizadeh K, Goya Grocin A, Song OR, Howell M, Calado DP, Tate EW, Validation and Invalidation of Chemical Probes for the Human N-myristoyltransferases. Cell Chem Biol, 26(6):892-900.e4(2019) [pubmed]

curator keyword: Technical

submitter keyword: N-myristoylation, myristic acid alkyne YnMyr, metabolic tagging, IMP-366 (DDD85646), IMP-1088, 2-hydroxymyristic acid, D-NMAPPD (B13), Tris-DBA palladium, chemical proteomics

Edward W. Tate
contact affiliation	Department of Chemistry, Imperial College London, Molecular Research Science Hub, 80 Wood Lane, London W12 0BZ, United Kingdom. The Francis Crick Institute, 1 Midland Road, London NW1 1AT, United Kingdom.
contact email	e.tate@imperial.ac.uk
lab head
Wouter Kallemeijn
contact affiliation	Imperial College London
contact email	w.kallemeijn@imperial.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/11/PXD012722

PRIDE project URI

• PRIDE
  1. PXD012722
     1. Label: PRIDE project
     2. Name: Validation and invalidation of chemical probes for the human N-myristoyltransferases.