HISTIDINE-BASED ZINC-BINDING SEQUENCES AND THE ANTIMICROBIAL ACTIVITYOF CALPROTECTIN

Calprotectin is a protein in neutrophil cytoplasm and abscess fluids t hat appears to inhibit microbial growth through competition for zinc. This study was undertaken to identify specific sites that might be res ponsible for the protein's zinc-binding antimicrobial activity. A revi ew of published calprotectin amino acid sequences revealed the HEXXH m otif of thermolysin-type metalloproteases and an HHH polyhistidine seq uence near the C-terminus of the protein's heavy chain. Reagent polyhi stidine had antimicrobial activity against Candida albicans similar to that of calprotectin. Also, one type of HEXXH-containing thermolysin was inactive in the C. albicans assay, whereas a protein tagged with s ix C-terminal histidines did have calprotectin-like zinc-reversible an timicrobial activity. The activity of polyhistidine, as well as that o f calprotectin itself, was reversed by addition of zinc or treatment w ith the histidine-modifying compound diethylpyrocarbonate. These resul ts suggest that calprotectin's antimicrobial activity may be related t o certain histidine-based zinc-binding sequences.