Peptidase Family U34 Belongs to the Superfamily of N-terminal Nucleophile Hydrolases

Protein Sci. 2003 May;12(5):1131-5. doi: 10.1110/ps.0240803.


Peptidase family U34 consists of enzymes with unclear catalytic mechanism, for instance, dipeptidase A from Lactobacillus helveticus. Using extensive sequence similarity searches, we infer that U34 family members are homologous to penicillin V acylases (PVA) and thus potentially adopt the N-terminal nucleophile (Ntn) hydrolase fold. Comparative sequence and structural analysis reveals a cysteine as the catalytic nucleophile as well as other conserved residues important for catalysis. The PVA/U34 family is variable in sequence and exhibits great diversity in substrate specificity, to include enzymes such as choloyglycine hydrolases, acid ceramidases, isopenicillin N acyltransferases, and a subgroup of eukaryotic proteins with unclear function.

MeSH terms

  • Amidohydrolases / chemistry*
  • Bacterial Proteins / chemistry
  • Databases, Protein
  • Penicillin Amidase / chemistry*
  • Peptide Hydrolases / chemistry*
  • Sequence Alignment
  • Sequence Homology
  • Structural Homology, Protein
  • Substrate Specificity


  • Bacterial Proteins
  • Peptide Hydrolases
  • Amidohydrolases
  • N-terminal nucleophile hydrolase
  • Penicillin Amidase