The Crystal Structure ofHelicobacter pyloriCysteine-rich Protein B Reveals a Novel Fold for a Penicillin-binding Protein
Journal of Biological Chemistry
Colonization of the gastric mucosa with the spiralshaped Gram-negative proteobacterium Helicobacter pylori is probably the most common chronic infection in humans. The genomes of H. pylori strains J99 and 26695 have been completely sequenced. Functional and threedimensional structural information is available for less than one third of all open reading frames. We investigated the function and three-dimensional structure of a member from a family of cysteine-rich hypothetical proteins that are
... proteins that are unique to H. pylori and Campylobacter jejuni. The structure of H. pylori cysteine-rich protein (Hcp) B possesses a modular architecture consisting of four ␣/␣-motifs that are cross-linked by disulfide bridges. The Hcp repeat is similar to the tetratricopeptide repeat, which is frequently found in protein/protein interactions. In contrast to the tetratricopeptide repeat, the Hcp repeat is 36 amino acids long. HcpB is capable of binding and hydrolyzing 6-amino penicillinic acid and 7-amino cephalosporanic acid derivatives. The HcpB fold is distinct from the fold of any known penicillinbinding protein, indicating that the Hcp proteins comprise a new family of penicillin-binding proteins. The putative penicillin binding site is located in an amphipathic groove on the concave side of the molecule. The large number of protein sequences that have been derived by more than 80 genome sequencing projects of archaea, bacteria, and eukaryotes (www.cbs.dtu.dk/services/GenomeAtlas/) has provided the scientific community with sequences where neither a function nor a three-dimensional structure is available. These sequences, which are annotated as "hypothetical proteins," will become a rich source of information, provided that their structures and biological functions are investigated. Here we present the structure and function analysis of a hypothetical protein from the pathogenic microorganism Helicobacter pylori. Several implications of H. pylori on human health have been established since its discovery in 1983 by Warren and Marshal (1). It is generally accepted that gastric diseases such as duodenal ulcers, gastric ulcers, adenocarcinoma of the distal stomach, and gastric mucosa-associated lymphoid tissue lymphoma are caused by H. pylori, and its implication in extradigestive diseases is under discussion.