PXD046399 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-10-25 14:15:05 | ID requested | |
⏵ 1 | 2024-06-22 08:29:50 | announced | |
Publication List
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] |
Keyword List
submitter keyword: thermal proteome profiling,snake venom, metalloprotease |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD046399
- Label: PRIDE project
- Name: Assessing Target Specificity of the Small Molecule Inhibitor Marimastat to Snake Venom Toxins: A Novel Application of Thermal Proteome Profiling