engleski

Prokaryotic homologs help to define consensus sequences in metallopeptidase family M49

Metallopeptidases are the most diverse of the four main catalytic types of peptidases, with 53 families identified to date (MEROPS: the protease database). Family M49 (dipeptidyl peptidase III family) has been recognized as a distinct group based on 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 intracellular protein catabolism of eukaryotes. Our results indicated that enhanced expression of human DPP III might be used as biochemical marker for endometrial and ovarian cancer. 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. Assuming that the new data of genomes sequencing also contain unknown members of M49 family, we have performed the similarity search and revealed 14 homologous protein sequences, two of them prokaryotic, whose multiple alignment gave five highly conserved regions. By additional manual stringency, two conserved linear motifs 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 evolutionary 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 α -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.

M49 family; consensus sequence; metallopeptidase; dipeptidy peptidase III

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