PXD044971-1

PXD044971 is an original dataset announced via ProteomeXchange.

Title	Selective Arylation of Selenocysteine of Thioredoxin Reductase 1 by an Organogold Compound: Expanding the Tool-Box of Metal-Templated Reactions in Cancer Cells – pull-down
Description	Cyclometalated gold(III) complexes have been reported to template C-S cross-coupling reactions in a biological environment and acting as modifies of cysteine residues. To broaden the scope of organogold complexes for covalent protein post-translational modification in cancer cells, an oxime-containing C^N-cyclometalated gold(III) compound was synthesised featuring a carboxylic acid group for either immobilisation on amine-bearing solid support (Au), or functionalisation with a fluorescent tag (Au-Fluo). Live-cell imaging revealed that Au-Fluo distributed evenly into SW480 colon carcinoma cells, with a slight preference for the nuclear and nucleolar compartments. Thioredoxin reductase 1 (TXNRD1) was observed as the major interactor from whole cell lysates of SW480 cells in chemoproteomic approaches and a 2 : 1 binding stoichiometry resulted from titration-dependent pull-downs. Direct interactions confirmed a high reactivity of Au towards the catalytic CysSec-dyad at the C-terminus of TXNRD1 and revealed double arylation events at this motif. Therefore, the observed Au-templated arylation of selenocysteine likely contributes to the compound’s biological effects. Proteome profiling of SW480 cancer cells treated with sub-cytotoxic concentrations of Au revealed an apparent reduction of the available selenium pool by down-regulating the detected selenoproteins, except TXNRD1. Additionally, Au treatment induced the NRF2-KEAP1 stress response, pointing towards a disturbance of the intracellular redox balance by Au-mediated covalent targeting of TXNRD1. Inhibition of heme oxygenase-1 (HMOX1), the most strongly induced NRF2-target, showed pronounced synergism with Au treatment. Overall, organogold compounds, templating the formation of C–S(Se) bonds in cells as a novel mode of action, hold promise for the targeted modification of (onco)proteins.
HostingRepository	PRIDE
AnnounceDate	2025-04-22
AnnouncementXML	Submission_2025-04-22_05:04:42.417.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christopher Gerner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-30 08:18:35	ID requested
⏵ 1	2025-04-22 05:04:42	announced

10.1016/J.XCRP.2024.102072;

submitter keyword: arylation ∙ cancer ∙ chemoproteomics ∙ gold ∙ metals in medicine ∙ selenoprotein ∙ thioredoxin reductase 1

Christopher Gerner
contact affiliation	University of Vienna, Faculty of Chemistry, Department of Analytical Chemistry
contact email	christopher.gerner@univie.ac.at
lab head
Christopher Gerner
contact affiliation	University of Vienna
contact email	christopher.gerner@univie.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044971
     1. Label: PRIDE project
     2. Name: Selective Arylation of Selenocysteine of Thioredoxin Reductase 1 by an Organogold Compound: Expanding the Tool-Box of Metal-Templated Reactions in Cancer Cells – pull-down