CysDB: a human cysteine database based on experimental quantitative chemoproteomics

Lisa M Boatner; Maria F Palafox; Devin K Schweppe; Keriann M Backus

doi:10.1016/j.chembiol.2023.04.004

CysDB: a human cysteine database based on experimental quantitative chemoproteomics

Cell Chem Biol. 2023 Jun 15;30(6):683-698.e3. doi: 10.1016/j.chembiol.2023.04.004. Epub 2023 Apr 28.

Authors

Lisa M Boatner¹, Maria F Palafox², Devin K Schweppe³, Keriann M Backus⁴

Affiliations

¹ Biological Chemistry Department, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Department of Genome Sciences, University of Washington, Seattle, WA 98185, USA.
⁴ Biological Chemistry Department, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; DOE Institute for Genomics and Proteomics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: kbackus@mednet.ucla.edu.

Abstract

Cysteine chemoproteomics provides proteome-wide portraits of the ligandability or potential "druggability" for thousands of cysteine residues. Consequently, these studies are facilitating resources for closing the druggability gap, namely, achieving pharmacological manipulation of ∼96% of the human proteome that remains untargeted by U.S. Food and Drug Administration (FDA) approved small molecules. Recent interactive datasets have enabled users to interface more readily with cysteine chemoproteomics datasets. However, these resources remain limited to single studies and therefore do not provide a mechanism to perform cross-study analyses. Here we report CysDB as a curated community-wide repository of human cysteine chemoproteomics data derived from nine high-coverage studies. CysDB is publicly available at https://backuslab.shinyapps.io/cysdb/ and features measures of identification for 62,888 cysteines (24% of the cysteinome), as well as annotations of functionality, druggability, disease relevance, genetic variation, and structural features. Most importantly, we have designed CysDB to incorporate new datasets to further support the continued growth of the druggable cysteinome.

Keywords: Cysteine; chemoproteomics; covalent probes; cysteinome; database; electrophilic fragments; ligandability; multi-omics.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Cysteine* / chemistry
Humans
Proteome* / chemistry

Substances

Cysteine
Proteome

Grants and funding

T32 GM008185/GM/NIGMS NIH HHS/United States