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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.

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This article was published in the following journal.

Name: Biochemistry
ISSN: 1520-4995
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The small ribonucleoprotein component of RIBOSOMES. It contains the MESSENGER RNA binding site and two TRANSFER RNA binding sites - one for the incoming AMINO ACYL TRNA (A site) and the other (P site) for the peptidyl tRNA carrying the elongating peptide chain.

An enzyme that transfers acyl groups from acyl-CoA to glycerol-3-phosphate to form monoglyceride phosphates. It acts only with CoA derivatives of fatty acids of chain length above C-10. Also forms diglyceride phosphates. EC 2.3.1.15.

A group of compounds which consist of a nucleotide molecule to which an additional nucleoside is attached through the phosphate molecule(s). The nucleotide can contain any number of phosphates.

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An NAD-dependent enzyme that catalyzes the oxidation of acyl-[acyl-carrier protein] to trans-2,3-dehydroacyl-[acyl-carrier protein]. It has a preference for acyl groups with a carbon chain length between 4 to 16.

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