Analysis of Cysteine Redox Post-Translational Modifications in Cell Biology and Drug Pharmacology.
Reversible cysteine oxidation is an emerging class of protein post-translational modification (PTM) that regulates catalytic activity, modulates conformation, impacts protein-protein interactions, and affects subcellular trafficking of numerous proteins. Redox PTMs encompass a broad array of cysteine oxidation reactions with different half-lives, topographies, and reactivities such as S-glutathionylation and sulfoxidation. Recent studies from our group underscore the lesser known effect of redox protein modifications on drug binding. To date, biological studies to understand mechanistic and functional aspects of redox regulation are technically challenging. A prominent issue is the lack of tools for labeling proteins oxidized to select chemotype/oxidant species in cells. Predictive computational tools and curated databases of oxidized proteins are facilitating structural and functional insights into regulation of the network of oxidized proteins or redox proteome. In this chapter, we discuss analytical platforms for studying protein oxidation, suggest computational tools currently available in the field to determine redox sensitive proteins, and begin to illuminate roles of cysteine redox PTMs in drug pharmacology.
Oncology Research Unit, Pfizer Worldwide Research and Development, 10770 Science Center Drive, San Diego, CA, 92121, USA.
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Oncology Research Unit, Pfizer Worldwide Research and Development, 10770 Science Center Drive, San Diego, CA, 92121, USA. brion.murray@pfizer.com.
Brion W
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Murray
D019295:Computational Biology / Q000379:methods*; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D030562:Databases, Protein; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D020543:Proteome; D040901:Proteomics / Q000379:methods*; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism; D057386:Search Engine; D012984:Software; D064878:Web Browser; D057188:Workflow
D011506:Proteins; D020543:Proteome; D017382:Reactive Oxygen Species; D005978:Glutathione; D003545:Cysteine
Bioinformatics; Chemical probes; Cysteine; Proteomics; ROS; Redox states; S-glutathionylation; Sulfoxidation