title: Peptidase family U34 belongs to the superfamily of N-terminal nucleophile hydrolases.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Jimin
authors.initials: J
authors.lastname: Pei
authors.forename: Nick V
authors.initials: NV
authors.lastname: Grishin
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry; D030562:Databases, Protein; D010399:Penicillin Amidase / Q000737:chemistry*; D010447:Peptide Hydrolases / Q000737:chemistry*; D016415:Sequence Alignment; D017385:Sequence Homology; D040681:Structural Homology, Protein; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D010447:Peptide Hydrolases; D000581:Amidohydrolases; C438834:N-terminal nucleophile hydrolase; D010399:Penicillin Amidase