PEPTIDES CORRESPONDING TO THE REGION ADJACENT TO HIS-94 IN THE SMALL-SUBUNIT OF CYTOCHROME B(558) INHIBIT SUPEROXIDE GENERATION IN A CELL-FREE SYSTEM FROM HUMAN NEUTROPHILS

Synthetic peptides corresponding to the region adjacent to His-94 in t he small subunit of cytochrome b(558) inhibited superoxide generation in a cell-free system. The shortest sequence that gave a half inhibito ry concentration (IC50) lower than 50 mu M was TRNYYVRAVL. Substitutio n of alanine for any of two tyrosine or central valine residues marked ly increased IC50, thereby indicating that these residues are critical for the activity. Since the inhibition was observed when the peptide was added to the system before but not after the stimulation with sodi um dodecylsulfate, the peptides seem to interact irreversibly with the cytochrome molecule and hinder electron transport or to interfere wit h the association between cytochrome b(558) and cytosolic alternativel y components. (C) 1994 Academic Press, Inc.