The cysteine-rich protein a from Helicobacter pylori is a beta-lactamase

Among the large number of hypothetical proteins within the genomes of Helic obacter pylori, there is a family of unique and highly disulfide-bridged pr oteins, designated family 12, for which no function could originally be ass igned. Sequence analysis revealed that members of this family possess a mod ular architecture of alpha/beta-units and a stringent pattern of cysteine r esidues. The H. pylori cysteine-rich protein A (HcpA), which is a member of this family, was expressed and refolded from inclusion bodies. Six pairs o f cysteine residues, which are separated by exactly seven residues, form di sulfide bridges. HcpA is a beta-lactamase. It slowly hydrolyzes 6-aminopeni cillinic acid and 7-aminocephalosporanic acid (ACA) derivatives. The turnov er for 6-aminopenicillinic acid derivatives is 23 times greater than for AC A derivatives. The enzyme is efficiently inhibited by cloxacillin and oxaci llin but not by ACA derivatives or metal chelators, We suggest that all fam ily 12 members possess similar activities and might be involved in the synt hesis of the cell wall peptidoglycan. They might also be responsible for am oxicillin resistance of certain H. pylori strains.