PXD018825

PXD018825 is an original dataset announced via ProteomeXchange.

Title	Haloacetic Acids and Haloacetamides Attack Distinct Cellular Proteome Thiols
Description	Disinfection by-products (DBPs) exposure has been linked to multiple adverse health outcomes. However, the molecular initiating events by which DBPs induce their toxicities remains unclear. Herein we combined reporter cell lines and activity-based protein profiling (ABPP) chemical proteomics to identify protein targets of six haloacetic acids (HAAs) and haloacetamides (HAMs), on the proteome-wide level. While HAAs and HAMs had similar cytotoxicities, when compared to controls, the later has 12.5 times greater Nrf2-mediated oxidative stress response, demonstrating their distinct toxicity pathways. ABPP on crude cell lysates suggested that nonspecific proteome thiol reactivity correlates with cytotoxicity. Interestingly, live cell ABPP results revealed class-specific proteins attacked by HAMs or HAAs. Subsequent proteomics analysis identified >100 unique targets per DBP. HAMs showed preferential reactivity towards disulfide oxidoreductase enzymes, accounting for their stronger Nrf2 responses. To further probe alkylation mechanisms, we directly monitored protein adducts and identified 120 and 37 unique peptides with IAM and IAA adducts, respectively. Of the later we confirmed glyceraldhye-3-phosphate dehydrogenase (GAPDH) as a key target of IAA, specifically attacked at the catalytic Cys 152. This is the first study reporting the distinct cellular protein targets of HAAs and HAMs on the proteome-wide level, which highlights their different toxicity pathways despite their similar structures.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:14:52.171.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Hall
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	N-methylmaleimide modified L-cysteine; iodoacetic acid derivatized residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-27 01:14:35	ID requested
1	2020-11-11 09:13:37	announced
⏵ 2	2024-10-22 05:14:52	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Disinfection by-products

Proteomics

Protein adducts

GAPDH

Nrf2-Keap1

Hui Peng
contact affiliation	Department of Chemistry and School of the Environment, University of Toronto, Canada
contact email	hui.peng@utoronto.ca
lab head
David Hall
contact affiliation	University of Toronto
contact email	davidross.hall@mail.utoronto.ca
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/2020/11/PXD018825

PRIDE project URI

• PRIDE
  1. PXD018825
     1. Label: PRIDE project
     2. Name: Haloacetic Acids and Haloacetamides Attack Distinct Cellular Proteome Thiols