Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chemoproteomic profiling to identify Ophiobolin A targets

ABSTRACT: Cysteine and lysine chemoproteomic profiling of Ophiobolin A

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Lung Endothelial Cell

DISEASE(S): Lung Carcinoma

SUBMITTER: Daniel Nomura

LAB HEAD: Daniel Nomura

PROVIDER: PXD047763 | Pride | 2023-12-12

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	AG_NCI1703_OPA_isoTOP_210224_1_1.raw	Raw
	AG_NCI1703_OPA_isoTOP_210224_1_2.raw	Raw
	AG_NCI1703_OPA_isoTOP_210224_1_3.raw	Raw
	AG_NCI1703_OPA_isoTOP_210224_1_4.raw	Raw
	AG_NCI1703_OPA_isoTOP_210224_1_5.raw	Raw

Items per page:

1 - 5 of 61

Publications

Ophiobolin A Covalently Targets Complex IV Leading to Mitochondrial Metabolic Collapse in Cancer Cells.

Gowans Flor A FA Thach Danny Q DQ Wang Yangzhi Y Altamirano Poblano Belen E BE Dovala Dustin D Tallarico John A JA McKenna Jeffrey M JM Schirle Markus M Maimone Thomas J TJ Nomura Daniel K DK

bioRxiv : the preprint server for biology 20230309

Ophiobolin A (OPA) is a sesterterpenoid fungal natural product with broad anti-cancer activity. While OPA possesses multiple electrophilic moieties that can covalently react with nucleophilic amino acids on proteins, the proteome-wide targets and mechanism of OPA remain poorly understood in many contexts. In this study, we used covalent chemoproteomic platforms to map the proteome-wide reactivity of OPA in a highly sensitive lung cancer cell line. Among several proteins that OPA engaged, we focu ...[more]

PMID: 36945520

Similar Datasets

Chemoproteomics-Enabled Discovery of a Covalent Molecular Glue Degrader

Project description:Discovery of a covalent molecular glue degrader that covalently interacts with UBE2D and engages in molecular glue interactions with NFKB1

2023-02-08 | PXD039924 | Pride

Global profiling of phosphorylation-dependent changes in cysteine reactivity

Project description:Proteomics has revealed that the ~20,000 human genes engender a far greater number of proteins, or proteoforms, that are diversified in large part by post-translational modifications (PTMs). How such PTMs affect protein structure and function is an active area of research but remains technically challenging to assess on a proteome-wide scale. Here, we describe a chemical proteomic method to quantitatively relate serine/threonine phosphorylation to changes in the reactivity of cysteine residues, a parameter that can affect the potential for cysteines to be post-translationally modified or engaged by covalent drugs. Leveraging the extensive high-stoichiometry phosphorylation occurring in mitotic cells, we discover numerous cysteines that exhibit phosphorylation-dependent changes in reactivity on diverse proteins enriched in cell cycle regulatory pathways. The discovery of bidirectional changes in cysteine reactivity often occurring in proximity to serine/threonine phosphorylation events points to the broad impact of phosphorylation on the chemical reactivity of proteins and the future potential to create small-molecule probes that differentially target PTM-modified proteoforms.

2022-03-03 | PXD026730 | Pride

Targeted Protein Localization by Covalent 14-3-3 Recruitment

Project description:chemoproteomic profiling of covalent ligands that target 14-3-3

2024-08-28 | PXD054696 | Pride

Selective inhibitors of JAK1 targeting a subtype-restricted allosteric cysteine

Project description:The JAK family of non-receptor tyrosine kinases includes four subtypes (JAK1, JAK2, JAK3, and TYK2) and is responsible for signal transduction downstream of diverse cytokine receptors. JAK inhibitors have emerged as important therapies for immuno(onc)ological disorders, but their use is limited by undesirable side effects presumed to arise from poor subtype selectivity, a common challenge for inhibitors targeting the ATP-binding pocket of kinases. Here, we describe the chemical proteomic discovery of a druggable allosteric cysteine present in the non-catalytic pseudokinase domain of JAK1 (C817) and TYK2 (C838), but absent from JAK2 or JAK3. Electrophilic compounds selectively engaging this site block JAK1-dependent transphosphorylation and cytokine signaling, while appearing to act largely as “silent” ligands for TYK2. Importantly, the allosteric JAK1 inhibitors do not impair JAK2-dependent cytokine signaling and are inactive in cells expressing a C817A JAK1 mutant. Our findings thus reveal an allosteric approach for inhibiting JAK1 with unprecedented subtype selectivity.

2023-07-20 | PXD031384 | Pride

Chemoproteomic capture of RNA binding activity in living cells

Project description:Proteomic methods for RNA interactome capture (RIC) rely principally on crosslinking native or labeled cellular RNA to enrich and investigate RNA-binding protein (RBP) composition and function in cells. The ability to measure RBP activity at individual binding sites by RIC, however, has been more challenging due to the heterogenous nature of peptide adducts derived from the RNA-protein crosslinked site. Here, we present an orthogonal strategy that utilizes clickable electrophilic purines to directly quantify protein-RNA interactions on proteins through photoaffinity competition with 4-thiouridine (4SU)-labeled RNA in cells. Our photo-activatable-competition and chemoproteomic enrichment (PACCE) method facilitated detection of >5,500 cysteine sites across ~3,000 proteins displaying RNA-sensitive alterations in probe binding. Importantly, PACCE enabled functional profiling of canonical RNA-binding domains as well as discovery of moonlighting RNA binding activity in the human proteome. Collectively, we present a chemoproteomic platform for global quantification of protein-RNA binding activity in living cells.

2023-10-12 | GSE240318 | GEO

Monitoring Fe-S cluster occupancy across the E. coli proteome using chemoproteomics

Project description:Iron-sulfur (Fe-S) clusters are ubiquitous metallocofactors involved in redox chemistry, radical generation, and gene regulation. Common methods to monitor Fe-S clusters include spectroscopic analysis of purified proteins, and auto-radiographic visualization of radiolabeled iron distribution in proteomes. Here, we report a chemoproteomic strategy that monitors changes in the reactivity of Fe-S cysteine ligands to inform on Fe-S cluster occupancy. We highlight the utility of this platform in E. coli by: (1) demonstrating global disruptions in Fe-S incorporation in cells cultured under iron-depleted conditions; (2) determining Fe-S client proteins reliant on three scaffold/carrier proteins within the Isc Fe-S biogenesis pathway; and, (3) identifying two previously unannotated Fe-S proteins, TrhP and DppD. In summary, the chemoproteomic strategy described herein is a powerful tool that reports on Fe-S cluster incorporation directly within a native proteome, and enables the interrogation of Fe-S biogenesis pathways, and the identification of previously uncharacterized Fe-S proteins.

2024-05-22 | PXD026488 | Pride

LiP-Quant, an automated chemoproteomic approach to identify drug targets in complex proteomes, p3

Project description:LiP-Quant MS sample preparation for target deconvolution

2020-09-09 | PXD019902 | Pride

Multiplexed CuAAC-Suzuki-Miyaura for tandem activity-based chemoproteomic profiling

Project description:Suzuki-Miyauara cross-coupling has been used for mass-spectrometry-based chemoproteomics, including for target deconvolution and site of labeling studies. We also demonstrated that Suzuki-Miyauara cross coupling and CuAAC can be combined for dual target labeling for mass spectrometry-based proteomics. Furthermore, multiplexed CuAAC Suzuki-Miyaura chemoproteomics platform has been successfully applied to identify the protein targets of bifunctional cysteine- and lysine-reactive crosslinking probes.

2021-02-03 | PXD022279 | Pride