Presence of a motif conserved between helicobacter pylori TNF-α inducing protein (Tipα) and penicillin-binding proteins

Abstract

Here we report a primary structure conserved between Helicobacter pylori (H. pylori)-tumor necrosis factor-α inducing protein (Tipα) 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 Tipα has a carcinogenic potential as tumor promoter, and that it has no obvious homologue in other species. To investigate the structure-function relationship of Tipα and to predict its ancestral protein, we searched among proteins which have weak homology to Tipα in their primary structures, using Psi-Blast, and we identified numerous Gram-positive bacterial penicillin-binding proteins as weakly homologous to Tipα. Among these, several unique amino acids are conserved and form a motif-like structure. Phylogenic tree analysis indicated that Tipα is closer to the penicillin-binding proteins of Gram-positive bacteria, based on their primary structures, than to H. pylori. This finding suggests that Tipα and penicillin-binding proteins are derived from a common ancestral protein, and that Tipα gene may be transferred horizontally from Gram-positive bacteria to H. pylori. © 2005 Pharmaceutical Society of Japan.