PXD046399

PXD046399 is an original dataset announced via ProteomeXchange.

Title	Assessing Target Specificity of the Small Molecule Inhibitor Marimastat to Snake Venom Toxins: A Novel Application of Thermal Proteome Profiling
Description	New treatments that circumvent the pitfalls of traditional antivenom therapies are critical to address the problem of snakebite globally. Numerous snake venom toxin inhibitors have shown promising cross-species neutralization of medically significant venom toxins in vivo and in vitro. The development of high-throughput approaches for the screening of such inhibitors could accelerate their identification, testing, and implementation, and thus holds exciting potential for improving the treatments and outcomes of snakebite envenomation worldwide. Energetics-based proteomic approaches, including Thermal Proteome Profiling (TPP) and Proteome Integral Solubility Alteration (PISA), assays represent “deep proteomics” methods for high throughput, proteome-wide identification of drug targets and ligands. In the following study, we apply TPP and PISA methods to characterize the interactions between venom toxin proteoforms in Crotalus atrox (Western Diamondback Rattlesnake) and the snake venom metalloprotease (SVMP) inhibitor marimastat. We investigate its venom proteome-wide effects and characterize its interactions with specific SVMP proteoforms, as well as its potential targeting of non-SVMP venom toxin families. We also compare the performance of PISA thermal window and soluble supernatant with insoluble precipitate using two inhibitor concentrations, providing the first demonstration of the utility of a sensitive high-throughput PISA-based approach to assess the direct targets of small molecule inhibitors for snake venom.
HostingRepository	PRIDE
AnnounceDate	2024-06-22
AnnouncementXML	Submission_2024-06-22_08:29:49.304.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anthony Saviola
SpeciesList	scientific name: Crotalus atrox; NCBI TaxID: 8730;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-25 14:15:05	ID requested
⏵ 1	2024-06-22 08:29:50	announced

10.1016/j.mcpro.2024.100779;

Smith CF, Modahl CM, Ceja Galindo D, Larson KY, Maroney SP, Bahrabadi L, Brandehoff NP, Perry BW, McCabe MC, Petras D, Lomonte B, Calvete JJ, Castoe TA, Mackessy SP, Hansen KC, Saviola AJ, Assessing Target Specificity of the Small Molecule Inhibitor MARIMASTAT to Snake Venom Toxins: A Novel Application of Thermal Proteome Profiling. Mol Cell Proteomics, 23(6):100779(2024) [pubmed]

submitter keyword: thermal proteome profiling,snake venom, metalloprotease

Anthony Saviola
contact affiliation	University of Colorado Anschutz Medical Campus
contact email	anthony.saviola@cuanschutz.edu
lab head
Anthony Saviola
contact affiliation	University of Colorado Anschutz Medical Campus
contact email	anthony.saviola@cuanschutz.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD046399
     1. Label: PRIDE project
     2. Name: Assessing Target Specificity of the Small Molecule Inhibitor Marimastat to Snake Venom Toxins: A Novel Application of Thermal Proteome Profiling