Cleavage of phosphorylase kinase and calcium-free calmodulin by HIV-1 protease

• Published in: Biochemical and biophysical research communications Vol. 178; no. 3; pp. 892 - 898
• Main Authors: Daube, H., Billich, A., Mann, K., Schramm, H.J.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 15.08.1991; Elsevier
• Subjects: AIDS/HIV; Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Binding Sites; Biological and medical sciences; Calcium Chloride - pharmacology; calmodulin; Calmodulin - metabolism; Computer Simulation; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; HIV Protease - metabolism; HIV-1 - enzymology; human immunodeficiency virus 1; Hydrolases; Kinetics; Macromolecular Substances; Magnesium Chloride - pharmacology; Models, Molecular; Muscles - enzymology; phosphorylase kinase; Phosphorylase Kinase - metabolism; Protein Conformation; Rabbits; Recombinant Proteins - metabolism; Substrate Specificity; X-Ray Diffraction; Virus; Enzyme; Cleavage site; Proteinase; Molecular model; Retroviridae; Lentivirinae; Human immunodeficiency virus; Phosphorylase kinase; Subunit; Computer aid; Calmodulin
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/0006-291X(91)90975-D

Phosphorylase kinase and calcium-free calmodulin are digested by human immunodeficiency virus-1 protease. In phosphorylase kinase, the α subunit is preferentially hydrolyzed at arg 748-val 749. The β subunit is cleaved only slowly at leu 678-pro 679, and calmodulin, the integral δ subunit of phosphorylase kinase, is not cleaved at all. However, free calmodulin in the calcium-depleted form showed to be a good substrate for the protease. Here the cleavage occurs at phe 65-pro 66 and met 71-met 72. This fast hydrolysis of free calmodulin can be blocked by micromolar concentrations of Ca 2+ or millimolar concentrations of Mg 2+.