engleski

Prokaryotic homologs help to define consensus sequences in metallopeptidase family M49

In recent years the number of deduced amino acid sequences of metallopeptidases has increased dramatically revealing that these enzymes are the most diverse of the four main catalytic types of peptidases, with 51 families identified to date. Peptidase family M49 (dipeptidyl peptidase III family) has been recognized as a distinct group of metallopeptidases based on the significant similarity in primary structures of its members and the unique structural motif, hexapeptide HELLGH, which harbors the predicted active site residues. Dipeptidyl peptidase III (DPP III) was previously biochemically characterized as a cytosolic zinc-exopeptidase involved in the final steps of intracellular protein catabolism of eukaryotes. The regulatory role of DPP III in the metabolism of biologically active peptides (angiotensins and enkephalins) has been suggested. However, 3-D structure, physiological significance, regulation and distribution of this enzyme in the living world still need to be elucidated. Our results indicated that enhanced expression of DPP III might be used as biochemical marker for endometrial and ovarian cancer. We assumed that the new data of genomes sequencing also contain unknown members of this family and we attempted to define its evolutionary conserved amino acid sequence regions through the analysis of their primary structures. By the similarity search and additional manual stringency we have revealed 14 homologous protein sequences (members of family M49), two of them prokaryotic, whose multiple alignment gave five highly conserved regions. Two conserved linear motifs (consensus sequences) harboring four known active site residues of family M49 were defined as stretches of 16 and 6 amino acids located in the third and fourth conserved region. A part of sixteen-amino acid consensus sequence and the complete consensus sequence of six amino acid were predicted to reside in a alpha-helix. In conclusion, the most recent data on complete genome sequences helped us to reveal that metallopeptidase family M49 (DPP III family) is distributed in four kingdoms of organisms (Eubacteria, Protista, Fungi and Animalia), and to define two consensus sequences containing the active site residues. Bacterial homologs have been unexpected and so far confined to the proteins from one human symbiont and one oral pathogen.

consensus sequence ; dipeptidyl peptidase III ; M49 family ; metallopeptidase

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