PROSITE documentation PDOC00122

Serine carboxypeptidases, active sites

All known carboxypeptidases are either metallo carboxypeptidases or serine carboxypeptidases (EC 3.4.16.5 and EC 3.4.16.6). The catalytic activity of the serine carboxypeptidases, like that of the trypsin family serine proteases, is provided by a charge relay system involving an aspartic acid residue hydrogen-bonded to a histidine, which is itself hydrogen-bonded to a serine [1]. Proteins known to be serine carboxypeptidases are:

• Barley and wheat serine carboxypeptidases I, II, and III [2].
• Yeast carboxypeptidase Y (YSCY) (gene PRC1), a vacuolar protease involved in degrading small peptides.
• Yeast KEX1 protease, involved in killer toxin and α-factor precursor processing.
• Fission yeast sxa2, a probable carboxypeptidase involved in degrading or processing mating pheromones [3].
• Penicillium janthinellum carboxypeptidase S1 [4].
• Aspergullus niger carboxypeptidase pepF.
• Aspergullus satoi carboxypeptidase cpdS.
• Vertebrate protective protein / cathepsin A [5], a lysosomal protein which is not only a carboxypeptidase but also essential for the activity of both β-galactosidase and neuraminidase.
• Mosquito vitellogenic carboxypeptidase (VCP) [6].
• Naegleria fowleri virulence-related protein Nf314 [7].
• Yeast hypothetical protein YBR139w.
• Caenorhabditis elegans hypothetical proteins C08H9.1, F13D12.6, F32A5.3, F41C3.5 and K10B2.2.

This family also includes:

• Sorghum (s)-hydroxymandelonitrile lyase (EC 4.1.2.11) (hydroxynitrile lyase) (HNL) [8], an enzyme involved in plant cyanogenesis.

The sequences surrounding the active site serine and histidine residues are highly conserved in all these serine carboxypeptidases.