PXD027151 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: KDM7, proteomics, cyclic peptide, PTM |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD027151
- Label: PRIDE project
- Name: Plant homeodomain targeting cyclic peptides allosterically modulate KDM7 histone demethylase activity