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benzoquinone as a possible covalent modifier of an enzyme


"Substituent Effects on the Reactivity of Benzoquinone Derivatives with Thiols"
We study an enzyme that has an essential, nucleophilic cysteine residue.  In two organisms this enzyme is reversibly inhibited by 1,4-benzoquinone.  We were studying the same enzyme in a third organism.  My student performed a pre-incubation experiment with our enzyme on this compound.  These assays are typically used to detect covalent bond formation with concomitant inactivation of the enzyme.  They can be used whether or not the enzyme and inactivator have affinity for each other.  It appears that some inactivation is taking place.  What little I was able to turn up quickly makes the possibility of inactivation seem plausible, but I don't have much experience with how reactive 1,4-benzoquinones are.  Thoughts?

PMID: 31248982  PMCID: PMC6699853  DOI: 10.1074/jbc.RA119.008666
I did another quick search and found that benzoquinone also covalently modifies the nucleophilic cysteine residue in a protein tyrosine phosphatase enzyme.

"Moreover, the thiol reactivity of electrophilic quinones has also been highlighted by a fluorescence-based high throughput assay.31 In yet another example, 2,3-bis(2-hydroxyethylsulfanyl)naphthalene-1,4-dione was shown to inhibit the tumor marker S100B by forming a covalent bond with a cysteine residue.32 Taken together, these effects suggest that the naphthoquinone moiety and its heteroaromatic analogues might inhibit enzymatic activity via nonspecific interactions or by interfering with the redox chemistry of the cell via the depletion of its essential level of glutathione.33,34"
J. Med. Chem. 2016, 59, 497−503.  DOI: 10.1021/acs.jmedchem.5b00361

Quinones are quite reactive, being potent oxidants, and are known to deactivate enzymes and change protein function. They are also very photoactive and can participate in photochemistry, particularly electron transfer reactions, so you may want to consider that if your experiment is not protected from light.


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