Abstract
Eukaryotic aspartic proteases, such as pepsin, are synthesized as a single-chain zymogen. After activating into single-chain proteases, they contain bilobal structures. The three-dimensional structures of the N- and C-terminal lobes are homologous. It has been hypothesized that the origin of this internal similarity in eukaryotic aspartic proteases is derived from an evolutionary process of gene duplication and fusion (1). A primordial form of aspartic protease is probably a homodimer. The retroviral aspartic proteases are homodimers and structurally related to the eukaryotic aspartic proteases (2). Thus, the retroviral proteases may represent the primordial forms of eukaryotic enzymes. In this scenario, the gene of a homodimeric retroviral protease is integrated in the host genome of a primordial eukaryotic cell. The protease gene is retained by mutational processes which provided survival advantages to the host in evolution. It ultimately evolved through gene duplication and fusion to a single-chain, internally symmetrical eukaryotic enzyme.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Tang, J., James, M.N.G., Hsu, I.-N., Jenkins, J.A., and Blundell, T.L. (1978) “Structural Evidence for Gene Duplication in the Evolution of the Acid Protease” Nature 271:618–621.
Rao, J.K.M., Erickson, J.W., and Wlodawer, A. (1991) Structural and Evolutionary Relationships between Retroviral and Eucaryotic Aspartic Proteinases” Biochemistry 30:4663–4671.
Lin, X.L., Wong, R.N.S., and Tang, J. (1989) “Synthesis, Purification and Mutagenesis Studies of Recombinant Porcine Pepsinogen” J. Biol. Chem. 264:4482–4489.
Lin, Y.-Z., Fusek, M., Lin, X.L., Hartsuck, J.A., Kezdy, F.J., and Tang, J. (1992a) “pH Dependence of Kinetic Parameters of Pepsin, Rhizopuspepsin, and Their Active-site Hydrogen Bond Mutants” J. Biol. Chem. 267:18413–18418.
Lin, X.L., Lin, Y., Koelsch, G., Gustchina, A., Wlodawer, A., and Tang, J. (1992) “Enzymic Activities of Two-chain Pepsinogen, Two-chain Pepsin, and the Amino-terminal Lobe of Pepsinogen” J. Biol. Chem. 267:17257–17263.
Marciniszyn, J., Jr., Huang, J.S., Hartsuck, J.A., and Tang, J. (1976) “Mechanism of Intramolecular Activation of Pepsinogen” J. Biol. Chem. 251:7095–7102.
Lin, X.L., Loy, J. A., Sussman, R, and Tang, J. (1993) “Conformational Instability of the N- and C-terminal Lobes of Porcine Pepsin in Neutral and Alkaline Solutions” Protein Sci. 2:1383–1390.
Al-Janabi, J., Hartsuck, J.A., and Tang, J. (1972) “Kinetics and Mechanism of Pepsinogen Activation” J. Biol. Chem. 247:4628–4632.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Springer Science+Business Media New York
About this chapter
Cite this chapter
Lin, X., Tang, J. (1995). Rearranging Pepsinogen and Pepsin by Protein Engineering. In: Takahashi, K. (eds) Aspartic Proteinases. Advances in Experimental Medicine and Biology, vol 362. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1871-6_4
Download citation
DOI: https://doi.org/10.1007/978-1-4615-1871-6_4
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-5761-2
Online ISBN: 978-1-4615-1871-6
eBook Packages: Springer Book Archive