Sequence analysis of the aminoacylase-1 family. A new proposed signature for metalloexopeptidases

The amino acid sequence analysis of the human and porcine aminoacylases-1, the carboxypeptidase S precursor from Saccharomyces cerevisiae, the succiny l-diaminopimelate desuccinylase from Escherichia coli, Haemophilus influenz ae and Corynebacterium glutamicum, the acetylornithine deacetylase from Esc herichia coli and Dictyostelium discoideum and the carboxypeptidase G(2) pr ecursor from Pseudomonas strain, using the Basic Local Alignment Search Too l (BLAST) and the Position-Specific Iterated BLAST (PSI-BLAST), allowed us to suggest that all these enzymes, which share common functional and bioche mical features, belong to the same structural family. The three amino acid blocks which were found to be highly conserved, using the CLUSTAL W program , could be assigned to the catalytic active site, based on the general thre e-dimensional structure of the carboxypeptidase G(2) from the Pseudomonas s tr ain precursor. Six additional proteins with the same signature have been retrieved after performing two successive PSI-BLAST iterations using the s equence of the conserved motif, namely Lactobacillus delbrueckii aminoacyl- histidine dipeptidase, Streptomyces griseus aminopeptidase, Saccharomyces c erevisiae aminopeptidase Y precursor, two Bacillus stearothermophilus N-car bamyl-L-amino acid amidohydrolases and Pseudomonas sp. hydantoin utilizatio n protein C. The three conserved amino acid motifs corresponded to the foll owing blocks: (i) [S, G, A]-H-x-D-x-V; (ii) G-x-x-D; and (iii) x-E-E. This new sequence signature is clearly different from that commonly reported in the literature for proteins belonging to the ArgE/DapE/CPG2/YscS family. (C ) 2001 Elsevier Science Inc. All rights reserved.