title: The cysteine-rich protein A from Helicobacter pylori is a beta-lactamase.
abstract: Among the large number of hypothetical proteins within the genomes of Helicobacter pylori, there is a family of unique and highly disulfide-bridged proteins, designated family 12, for which no function could originally be assigned. Sequence analysis revealed that members of this family possess a modular architecture of alpha/beta-units and a stringent pattern of cysteine residues. The H. pylori cysteine-rich protein A (HcpA), which is a member of this family, was expressed and refolded from inclusion bodies. Six pairs of cysteine residues, which are separated by exactly seven residues, form disulfide bridges. HcpA is a beta-lactamase. It slowly hydrolyzes 6-aminopenicillinic acid and 7-aminocephalosporanic acid (ACA) derivatives. The turnover for 6-aminopenicillinic acid derivatives is 2-3 times greater than for ACA derivatives. The enzyme is efficiently inhibited by cloxacillin and oxacillin but not by ACA derivatives or metal chelators. We suggest that all family 12 members possess similar activities and might be involved in the synthesis of the cell wall peptidoglycan. They might also be responsible for amoxicillin resistance of certain H. pylori strains.
authors.affiliation: Biochemisches Institut, Universität Zürich, Winterthurer Strasse 190, 8057 Zürich, Switzerland. mittl@biocfebs.unizh.ch
authors.forename: P R
authors.initials: PR
authors.lastname: Mittl
authors.forename: L
authors.initials: L
authors.lastname: Lüthy
authors.forename: P
authors.initials: P
authors.lastname: Hunziker
authors.forename: M G
authors.initials: MG
authors.lastname: Grütter
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D003545:Cysteine; D004220:Disulfides; D019791:Guanidine; D016480:Helicobacter pylori / Q000201:enzymology* / Q000235:genetics; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D011489:Protein Denaturation; D017510:Protein Folding; D021382:Protein Sorting Signals / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D001618:beta-Lactamases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004220:Disulfides; D010446:Peptide Fragments; D021382:Protein Sorting Signals; D011994:Recombinant Proteins; C410728:hcpA protein, Helicobacter pylori; D001618:beta-Lactamases; D019791:Guanidine; D003545:Cysteine