Presence of a motif conserved between Helicobacter pylori TNF-alpha inducing protein (Tipalpha) and penicillin-binding proteins.

Here we report a primary structure conserved between Helicobacter pylori (H. pylori)-tumor necrosis factor-alpha inducing protein (Tipalpha) and bacterial penicillin-binding proteins. H. pylori is a Gram-negative bacterium which plays a key part in carcinogenesis in the human stomach. We previously reported that Tipalpha has a carcinogenic potential as tumor promoter, and that it has no obvious homologue in other species. To investigate the structure-function relationship of Tipalpha and to predict its ancestral protein, we searched among proteins which have weak homology to Tipalpha in their primary structures, using Psi-Blast, and we identified numerous Gram-positive bacterial penicillin-binding proteins as weakly homologous to Tipalpha. Among these, several unique amino acids are conserved and form a motif-like structure. Phylogenic tree analysis indicated that Tipalpha is closer to the penicillin-binding proteins of Gram-positive bacteria, based on their primary structures, than to H. pylori. This finding suggests that Tipalpha and penicillin-binding proteins are derived from a common ancestral protein, and that Tipalpha gene may be transferred horizontally from Gram-positive bacteria to H. pylori.