Pepsin homologues in bacteria

Homologues of the aspartic peptidase pepsin have been found in the completed genomic sequences from seven species of bacteria. The bacterial homologues, unlike those from eukaryotes, do not possess signal peptides, and would therefore be intracellular acting at neutral pH. The bacterial homologues have Thr218 replaced by Asp, a change which in renin has been shown to confer activity at neutral pH. No pepsin homologues could be detected in any archaean genome.The peptidase family A1 is found in some species of bacteria as well as eukaryotes. The bacterial homologues fall into two groups, one from oceanic bacteria and one from plant symbionts. The bacterial homologues are all predicted to be intracellular proteins, unlike the eukaryotic enzymes. The bacterial homologues are bilobed like pepsin, implying that if no horizontal gene transfer has occurred the duplication and fusion event might be very ancient indeed, preceding the divergence of bacteria and eukaryotes. It is unclear whether all the bacterial homologues are derived from horizontal gene transfer, but those from the plant symbionts probably are. The homologues from oceanic bacteria are most closely related to memapsins (or BACE-1 and BACE-2), but are so divergent that they are close to the root of the phylogenetic tree and to the division of the A1 family into two subfamilies.Peptidases are widespread enzymes that catalyse the hydrolysis of peptide bonds. Not only do peptidases hydrolyse proteins to amino acids and peptides for nutrition and recycling, but they also perform some of the most important post-translational processing events leading to the activation (or inactivation) of many other proteins, including other enzymes and peptide hormones. Over 2% of the protein coding genes in a genome encode peptidases, and there are over 500 peptidase genes in the human genome. Peptidases exist in at least six catalytic types, depending on the nature of the nucleophile in the catalytic reaction (either the hydrox