Interaction of calmodulin with the phosphofructokinase target sequence

Abstract
Ca4 · calmodulin (Ca4 · CaM) inhibits the glycolytic enzyme phosphofructokinase, by preventing formation of its active tetramer. Fluorescence titrations show that the affinity of complex formation of Ca4 · CaM with the key 21‐residue target peptide increases 1000‐fold from pH 9.0 to 4.8, suggesting the involvement of histidine and carboxylic acid residues. 1H NMR pH titration indicates a marked increase in pK a of the peptide histidine on complex formation and HSQC spectra show related pH‐dependent changes in the conformation of the complex. This unusually strong sensitivity of a CaM–target complex to pH suggests a potential functional role for Ca4 · CaM in regulation of the glycolytic pathway.