Dehomocysteinylation is catalysed by the sirtuin-2-like bacterial lysine deacetylase CobB

Area of Science:

• Biochemistry
• Molecular Biology
• Enzymology

Background:

• Hyperhomocysteinemia (elevated blood homocysteine) is an independent risk factor for cardiovascular diseases, neurodegenerative diseases, and birth defects.
• Protein N-homocysteinylation is a key mechanism contributing to hyperhomocysteinemia, but dehomocysteinylation processes and enzymes remain largely unknown.

Purpose of the Study:

• To investigate the mechanisms and regulation of dehomocysteinylation.
• To identify enzymes involved in the removal of homocysteine from proteins.

Main Methods:

• Studied the spontaneous dehomocysteinylation reaction.
• Investigated the role of -SH groups in the reaction.
• Utilized in vitro and in vivo assays to assess the enzymatic activity of CobB.

Main Results:

• Dehomocysteinylation is a spontaneous reaction inhibited by blocking -SH groups, crucial for non-enzymatic removal.
• CobB, a bacterial lysine deacetylase, was identified as catalyzing lysine dehomocysteinylation both in vitro and in vivo.
• CobB is the first identified prokaryotic enzyme responsible for dehomocysteinylation.

Conclusions:

• This study elucidates the spontaneous nature of dehomocysteinylation and the critical role of -SH groups.
• Identifies CobB as the first prokaryotic dehomocysteinylation enzyme, offering insights into homocysteine removal from proteins.
• Provides potential targets for developing methods to identify N-homocysteine proteins.