Overview of Pepsin‐like Aspartic Peptidases

Ben M. Dunn1

1 University of Florida College of Medicine, Gainesville
Publication Name:  Current Protocols in Protein Science
Unit Number:  Unit 21.3
DOI:  10.1002/0471140864.ps2103s25
Online Posting Date:  November, 2001
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library


The aspartic peptidase family of enzymes has been implicated in a variety of disease states, from stomach ulcers, to breast cancer, and even Alzheimer's Disease. This unit describes the major characteristics of the aspartic peptidases, including mechanism of action, subcellular and tissue localization, and biological substrate specificity.

PDF or HTML at Wiley Online Library

Table of Contents

  • Sequence Homologies and Evolutionary Relatedness
  • Catalytic Mechanism
  • Subcellular and Tissue Localization of Aspartic Proteinases
  • Biological and Intrinsic Substrate Specificity
  • Aspartic Peptidases and Disease
  • Recombinant Expression, Purification, and Assays of Aspartic Peptidases
  • Figures
PDF or HTML at Wiley Online Library


PDF or HTML at Wiley Online Library



Literature Cited

Literature Cited
   Barrett, A.J., Rawlings, N.D., and Woessner, J.F. 1998. The Handbook of Proteolytic Enzymes, pp. 799‐986. Academic Press, San Diego.
   Blundell, T.L., Jenkins, J.A., Sewell, B.T., Pearl, L.H., Cooper, J.B., Tickle, I.J., Veerapandian, B., and Wood, S.P. 1990. X‐ray analysis of aspartic proteinases: The 3‐dimensional structure at 2.1 A resolution of endothiapepsin. J. Mol. Biol. 211:919‐941.
   Davies, D.R. 1990. The structure and function of the aspartic proteinases. Annu. Rev. Biophys. Chem. 19:189‐215.
   Francis, S.E., Sullivan, D.J., and Goldberg, D.E. 1997. Hemoglobin metabolism in the malaria parasite. Plasmodium falciparum. Annu. Rev. Microbiol. 51:97‐123.
   Fraser, M.E., Strynadka, N.C.J., Bartlett, P.A., Hanson, J.E., and James, M.N.G. 1992. Crystallographic analysis of transition‐state minics bound to penicillopepsin‐phosphorus‐containing peptide analogs. Biochemistry 31:5201‐5214.
   Green, D.W., Aykent, S., Gierse, J.K., and Zupec, M.E. 1990. Substrate specificity of recombinant human renal renin: Effect of histidine in the P2 subsite on pH dependence. Biochemistry 29:3126‐3133.
   Kervinen, J., Tobin, G.J., Costa, J., Waugh, D.S., Wlodawer, A., and Zdanov, A. 1999. Crystal structure of plant aspartic proteinase prophytepsin: Inactivation and vacuolar targeting. EMBO J 18:3947‐3955.
   Orengo, C.A., Michie, A.D., Jones, S., Jones, D.T., Swindells, M.B., and Thornton, J.M. 1999. CATH: A hierarchic classification of protein domain structures. Structure 5:1093‐1108.
   Rawlings, N.D. and Barrett, A.J. 2000. MEROPS: The peptidase database. Nucl. Acids Res. 28:323‐325.
   Rochefort, H., Garcia, M., Glondu, M., Laurent, V., Liaudet, E., Rey, J.M., and Roger, P. 2000. Cathepsin D in breast cancer: Mechanisms and clinical applications, a 1999 overview. Clin. Chim. Acta 291:157‐170.
   Saku, T., Sakai, H., Shibata, Y., Kato, Y., and Yamamoto, K. 1991. An immunocytochemical study on distinct intracellular localization of cathepsin D and cathepsin D in human gastric cells and various rat cells. J. Biochem. 110:956‐964.
   Sinha, S., Anderson, J.P., Barbour, R., Basi, G.S., Caccavello, R., Davis, D., Doan, M., Dovey, H.F., Frigon, N., Hong, J., Jacobson‐Croak, K., Jewett, N., Keim, P., Knops, J., Lieberburg, I., Power, M., Tan, H., Tatsuno, G., Tung, J., Schenk, D., Seubert, P., Suomensaari, S.M., Wang, S.W., Walker, D., Zhao, J., McConlogue, L., and John, V. 1999. Purification and cloning of amyloid precursor protein beta‐secretase from human brain. Nature 402:537‐540.
   Varis, K., Kekki, M., Harkonen, M., Sipponen, P., and Samloff, I.M. 1991. Serum pepsinogen‐1 and serum gastrin in the screening of atrophic pangastritis with high risk of gastric cancer. Scand. J. Gastroenterol. 26:117‐113.
   Veerapandian, B., Cooper, J.B., Sali, A., Blundell, T.L., Rosati, R.L., Dominy, B.W., Damon, D.B., and Hoover, D.J. 1992. Direct observation by x‐ray analysis of the tetrahedral intermediate of aspartic proteinases. Protein Sci. 1:322‐328.
Key Reference
   Barrett et al., 1998. See above.
  The definitive compilation of facts for the peptidase world. Authoritative but concise reviews by experts on each enzyme, all presented in a common format, make this a must‐have for any laboratory involved in proteolytic enzymes.
Internet Resource
  MEROPS website.
PDF or HTML at Wiley Online Library