PROSITE documentation PDOC00613

ArgE / dapE / ACY1 / CPG2 / yscS family signatures

The following enzymes have been shown [1,2,3] to be evolutionary and functionally related:

• In the biosynthetic pathway from glutamate to arginine, the removal of an acetyl group from N2-acetylornithine can be catalyzed via two distinct enzymatic strategies depending on the organism. In some bacteria and in fungi, the acetyl group is transferred on glutamate by glutamate N-acetyltransferase (EC 2.3.1.35) while in enterobacteria such as Escherichia coli, it is hydrolyzed by acetylornithine deacetylase (EC 3.5.1.16) (acetylornithinase) (AO) (gene argE). AO is a homodimeric cobalt-dependent enzyme which displays broad specificity and can also deacylates substrates such as acetylarginine, acetylhistidine, acetylglutamate semialdehyde, etc.
• Succinyldiaminopimelate desuccinylase (EC 3.5.1.18) (SDAP) (gene dapE) is the enzyme which catalyzes the fifth step in the biosynthesis of lysine from aspartate semialdehyde: the hydrolysis of succinyl-diaminopimelate to diaminopimelate and succinate. SDAP is an enzyme that requires cobalt or zinc as a cofactor.
• Aminoacylase-1 [4] (EC 3.5.1.14) (N-acyl-l-amino-acid amidohydrolase) (ACY1). ACY1 is a homodimeric zinc-binding mammalian enzyme that catalyzes the hydrolysis of N-α-acylated amino acids (except for aspartate).
• Carboxypeptidase G2 (EC 3.4.17.11) (folate hydrolase G2) (gene cpg2) from Pseudomonas strain RS-16. This enzyme catalyzes the hydrolysis of reduced and non-reduced folates to pteroates and glutamate. G2 is a homodimeric zinc-dependent enzyme.
• Vacuolar carboxypeptidase S (EC 3.4.17.4) (yscS) from yeast (gene CPS1).
• Peptidase T (EC 3.4.11.-) (gene pepT) (tripeptidase) from bacteria. This enzyme catalyzes a variety of tripeptides containing N-terminal methionine, leucine, or phenylalanine.
• Xaa-His dipeptidase (EC 3.4.13.3) (carnosinase) from Lactobacillus (gene pepV) [5], a metalloenzyme with activity against β-alanyl-dipeptides including carnosine (β-alanyl-histidine).

These enzymes share a few characteristics. They hydrolyse peptidic bonds in substrates that share a common structure, they are dependent on cobalt or zinc for their activity and they are proteins of 40 Kd to 60 Kd with a number of regions of sequence similarity.

As signature patterns for these proteins, we selected two of the conserved regions. The first pattern contains a conserved histidine which could be involved in binding metal ions and the second pattern contains a number of conserved charged residues.