Abstract
A proposed mechanism for the catalytic hydrolysis of peptide bonds by acid proteases is similar in many respects to the Zn–carbonyl mechanism previously derived for carboxypeptidase A. In the acid proteases the electrophilic component is the proton shared by Asp-32 and Asp-215; Tyr-75 donates its proton to the amide nitrogen of the scissile bond and an OH− ion from a water molecule bound between the carboxyl group of Asp-32 and the substrate attacks the carbonyl carbon atom.
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Hsu, I.-N., Delbaere, L. T. J., James, M. N. G. & Hofmann, T., Nature 266, 140–145 (1977).
Subramanian, E. et al. Proc. natn. Acad. Sci. U.S.A. 74, 556–559 (1977).
Fruton, J. S., Adv. Enzym. 44, 1–36 (1976).
Hsu, I.-N., Hofmann, T., Nyburg, S. C. & James, M. N. G., Biochem. biophys. Res. Commun. 72, 363–368 (1976).
Codding, P. W., Delbaere, L. T. J., Hayakawa, K., Hutcheon, W. L. B., James, M. N. G. & Jurasek, L., Can. J. Biochem. 52, 208–220 (1974).
Delbaere, L. T. J., Hutcheon, W. L. B., James, M. N. G. & Thiessen, W. E., Nature 257, 758–763 (1975).
Blow, D. M. & Crick, F. H. C., Acta Crystallogr. 12, 794–802 (1959).
Cunningham, A. et al. Can. J. Biochem. 54, 902–914 (1976).
Hartsuck, J. A. & Tang, J., J. biol. Chem. 247, 2575–2580 (1972).
Chen, K. C. S. & Tang, J., J. biol. Chem. 247, 2566–2574 (1972).
Lipscomb, W. N. et al. Brookhaven Symp. Biol. 21, 24–90 (1968).
Quiocho, F. A. & Lipscomb, W. N., Adv. Protein Chem. 25, 1–78 (1971).
Wang, T. T., Dorrington, K. J. & Hofmann, T., Biochem. biophys. Res. Commun. 57, 865–869 (1974).
Parker, R. E. & Isaacs, N. S., Chem. Rev. 59, 737–799 (1959).
Blow, D. M., Acc. Chem. Res. 9, 145–152 (1976).
Takahashi, M. & Hofmann, T., Biochem. J. 147, 549–563 (1975).
Sepulveda, P., Marciniszyn, J., Liu, D. & Tang, J., J. biol. Chem. 250, 5082–5088(1975).
Knowles, J. R., Phil. Trans. R. Soc. B 257, 135–146 (1970).
Kitson, T. M. & Knowles, J. R., FEBS Lett. 16, 337–338 (1971).
Huang, W.-Y. & Tang, J., Fedn Proc. 30, 759 (1971).
Rühlmann, A., Kukla, D., Schwager, P., Bartels, K. & Huber, R., J. molec. Biol. 77, 417–426(1973).
Sweet, R. M., Wright, H. T., Janin, J., Chothia, C. H. & Blow, D. M., Biochemistry 13, 4212–4228 (1974).
Dreath, J., Jansonius, J. N., Koekoek, R. & Wolthers, B. G., Adv. Protein Chem. 25, 79–115 (1971).
Newmark, A. K. & Knowles, J. R., J. Am. chem. Soc. 97, 3557–3559 (1975).
Kaiser, E. T. & Kaiser, B. L., Accts Chem. Res. 5, 219–224 (1972).
Fruton, J. S., Accts Chem. Res. 7, 241–246 (1974).
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James, M., Hsu, IN. & Delbaere, L. Mechanism of acid protease catalysis based on the crystal structure of penicillopepsin. Nature 267, 808–813 (1977). https://doi.org/10.1038/267808a0
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DOI: https://doi.org/10.1038/267808a0
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