Abstract
The Src Family Kinases (SFKs) are pivotal regulators of cellular signal transduction and highly sought-after targets in drug discovery. Their actions within cells are controlled by alterations in protein phosphorylation that switch the SFKs from autoinhibited to active states. The SFKs are also well recognized to contain redox-active cysteine residues where oxidation of certain residues directly contribute to kinase function. To more completely understand the factors that influence cysteine oxidation within the SFKs, a review is presented of the local structural environments surrounding SFK cysteine residues compared to their quantified oxidation in vivo from the Oximouse database. Generally, cysteine local structure and degree of redox sensitivity vary with respect to sequence conservation. Cysteine residues found in conserved positions are more mildly redox-active as they are found in hydrophobic environments and not fully exposed to solvent. Non-conserved redox-active cysteines are generally the most reactive with direct solvent access and/or in hydrophilic environments. Results from this analysis motivate future efforts to conduct comprehensive proteome-wide analysis of redox-sensitivity, conservation, and local structural environments of proteins containing reactive cysteine residues.