Cysteine S-conjugate sulfoxide β-lyase activity for human ACCS

Area of Science:

• Biochemistry
• Molecular Biology
• Enzymology

Background:

• 1-Aminocyclopropane-1-carboxylate synthase (ACCS) is known to catalyze a rate-limiting step in plant ethylene biosynthesis.
• A human gene encoding a putative ACCS protein was identified but lacks canonical ACC synthase activity, leaving its function unknown.
• The true biological role of human ACCS has remained an enigma for two decades.

Purpose of the Study:

• To elucidate the biochemical function of the human ACCS protein.
• To investigate the enzymatic activity of human ACCS using a biochemical profiling approach.
• To understand the structure-function relationship of human ACCS and identify key active site residues.

Main Methods:

• Biochemical profiling of human ACCS.
• Structure-function relationship studies guided by AlphaFold2 modeling.
• Analysis of mammalian ACCS homologs.

Main Results:

• Human ACCS exhibits cysteine conjugate sulfoxide β-lyase activity.
• This newly identified β-lyase activity is analogous to ACCS proteins in non-seed plants.
• Key active site residues crucial for the β-lyase activity were identified through structure-function analysis.
• Insights into the function of other mammalian ACCS homologs were gained.

Conclusions:

• Human ACCS possesses a distinct enzymatic function as a cysteine conjugate sulfoxide β-lyase, not a canonical ACC synthase.
• The identified β-lyase activity provides a new perspective on the enzyme's role in mammalian biology.
• Understanding the structure-function of human ACCS opens avenues for further research into its physiological relevance and that of related mammalian proteins.