PXD027151

PXD027151 is an original dataset announced via ProteomeXchange.

Title	Plant homeodomain targeting cyclic peptides allosterically modulate KDM7 histone demethylase activity
Description	Here we report the discovery of a set of potent de-novo cyclic peptides (CPs) targeting different binding sites on KDM7B. One CP (OC9) bound directly to the KDM7 PHD-finger, as supported by bio-layer interferometry (BLI), isothermal calorimetry (ITC), hydrogen-deuterium exchange mass spectrometry (HDxMS) and NMR studies, and was highly selective for KDM7s over other PHD-fingers. OC9 disrupted PHD-finger binding to H3K4me3, and allosterically modulated KDM7 demethylase activity at H3K9me2 site on peptides and histone extracts demonstrating PHD-finger targeting is as JmjC-domain targeted inhibitors, but more selective for specific KDM7 subfamily member and certain combinatorial histone PTM signatures. Proteomic analysis confirmed OC9 to selectively target KDM7 in nuclear lysates demonstrating its high affinity and selectivity against other H3K4me3 reader domains and KDMs.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:02:42.275.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jennifer Ward
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-07 02:17:14	ID requested
1	2023-07-20 10:47:50	announced
⏵ 2	2023-11-14 09:02:50	announced	2023-11-14: Updated project metadata.

Coleman OD, Macdonald J, Thomson B, Ward JA, Stubbs CJ, McAllister TE, Clark S, Amin S, Cao Y, Abboud MI, Zhang Y, Sanganee H, Huber KVM, Claridge TDW, Kawamura A, Cyclic peptides target the aromatic cage of a PHD-finger reader domain to modulate epigenetic protein function. Chem Sci, 14(26):7136-7146(2023) [pubmed]

submitter keyword: KDM7, proteomics, cyclic peptide, PTM

Kilian Huber
contact affiliation	Centre for medicines discovery, University of Oxford
contact email	kilian.huber@cmd.ox.ac.uk
lab head
Jennifer Ward
contact affiliation	University of Oxford
contact email	jawtdi@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027151
     1. Label: PRIDE project
     2. Name: Plant homeodomain targeting cyclic peptides allosterically modulate KDM7 histone demethylase activity