Chemoproteomics Using Nucleotide Acyl Phosphates Reveals an ATP-Binding Site at the Dimer Interface of Procaspase-6.

08:00 EDT 16th May 2019 | BioPortfolio

Summary of "Chemoproteomics Using Nucleotide Acyl Phosphates Reveals an ATP-Binding Site at the Dimer Interface of Procaspase-6."

Acyl phosphates of ATP (ATPAc) and related nucleotides have proven useful for the interrogation of known nucleotide binding sites via specific acylation of conserved lysines (K). In addition, occasional K-acylations are identified in proteins without such known sites. Here we present a robust and specific acylation of procaspase-6 by ATPAc at K133 in Jurkat cell lysates. The K133 acylation is dependent on π-π stacking interactions between the adenine moiety of ATPAc and a conserved Y198-Y198 site formed at the homodimeric interface of procaspase-6. Significantly, the Y198A mutation in procaspase-6 abolishes K133 acylation but has no effect on the proteolytic activity of the mature, active caspase-6 Y198A variant. Additional in vitro studies show that ATP can inhibit the auto-proteolytic activation of procaspase-6. These observations suggest that ATP, and possibly other nucleotides, may serve as the endogenous ligands for the allosteric site at the procaspase-6 dimer interface, a site which has persisted in "orphan" status for over a decade.


Journal Details

This article was published in the following journal.

Name: Biochemistry
ISSN: 1520-4995


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