title: The crystal structure of Helicobacter pylori cysteine-rich protein B reveals a novel fold for a penicillin-binding protein.
abstract: Colonization of the gastric mucosa with the spiral-shaped 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 three-dimensional 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 unique to H. pylori and Campylobacter jejuni. The structure of H. pylori cysteine-rich protein (Hcp) B possesses a modular architecture consisting of four alpha/alpha-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 penicillin-binding 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.
authors.affiliation: Biochemisches Institut, Universität Zürich, Winterthurer Strasse 190, 8057 Zürich, Switzerland.
authors.forename: Lucas
authors.initials: L
authors.lastname: Luthy
authors.forename: Markus G
authors.initials: MG
authors.lastname: Grutter
authors.forename: Peer R E
authors.initials: PR
authors.lastname: Mittl
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D001426:Bacterial Proteins; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides; D004305:Dose-Response Relationship, Drug; D019791:Guanidine / Q000378:metabolism; D016480:Helicobacter pylori / Q000737:chemistry*; D006602:Hexosyltransferases; D006868:Hydrolysis; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D002267:Muramoylpentapeptide Carboxypeptidase / Q000737:chemistry*; D016366:Open Reading Frames; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D011485:Protein Binding; D017510:Protein Folding; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D014867:Water / Q000737:chemistry; D001618:beta-Lactamases / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D002352:Carrier Proteins; D004220:Disulfides; D046915:Penicillin-Binding Proteins; D014867:Water; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; C410728:hcpA protein, Helicobacter pylori; C452853:hcpB protein, Helicobacter pylori; D001618:beta-Lactamases; D019791:Guanidine; D003545:Cysteine