Trypsin: A case study in the structural determinants of enzyme specificity

Biological Chemistry

Volumn 377, Issue 7-8, 1996, Pages 465-470

  Hedstrom, Lizbeth ^a  

^a BRANDEIS UNIVERSITY   (United States)

Author keywords

Chymotrypsin; Protein engineering; Serine proteases

Indexed keywords

CHYMOTRYPSIN; MUTANT PROTEIN; PROTEINASE; TRYPSIN;

ACYLATION; BINDING SITE; CRYSTAL STRUCTURE; ENZYME CONFORMATION; ENZYME KINETICS; ENZYME SPECIFICITY; ENZYME STRUCTURE; GENETIC ENGINEERING; HYDROLYSIS; PRIORITY JOURNAL; PROTEIN TERTIARY STRUCTURE; SHORT SURVEY; X RAY CRYSTALLOGRAPHY;

ACYLATION; AMINO ACID SEQUENCE; KINETICS; MOLECULAR SEQUENCE DATA; PROTEIN CONFORMATION; SEQUENCE ALIGNMENT; SUBSTRATE SPECIFICITY; TRYPSIN;

EID: 0029832603     PISSN: 14316730     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Short Survey

References (22)

1. Blow, D.M. (1971). The structure of chymotrypsin.In P.D. Boyer, ed. The Enzymes, (New York: Academic Press), pp., 213-248.
2. Bode, W., and Schwager, P. (1975). The refined crystal structure of bovine β trypsin at 1.8 Å resolution. II. Crystallographic refinement, calcium binding site, benzamidine binding site and active site at pH 7.0. J. Mol. Biol. 98, 693-717.
3. Bone, R., Silen, J.L., and Agard, D.A. (1989). Structural plasticity broadens the specificity of an engineered protease. Science 339, 191-195.
4. Craik, C.S., Largman, C., Fletcher, T., Roczniak, S., Barr, P.J., Fletterick, R., and Butter, W.J. (1985). Redesigning trypsin: alteration of substrate specificity. Science 228, 291-297.
5. Graf, L., Craik, C.S., Patthy, A., Roczniak, S., Fletterick, R.J., and Rutter, W.J. (1987). Selective alteration of substrate specificity by replacement of the aspartic acid 189 with lysine in the binding pocket of trypsin. Biochemistry 26, 2616-2623.
6. Graf, L., Jancso, A., Szilagyi, L., Hegyi, G., Pinter, K., Naray-Szabo, G., Hepp, J., Medzihradsky, K., and Rutter, W.J. (1988). Electrostatic complementarity within the substrate binding pocket of trypsin. Proc. Natl. Acad. Sci., USA 85, 4961-4965.
7. Hedstrom, L., Szilagyi, L., and Rutter, W.J. (1992). Converting trypsin to chymotrypsin: the role of surface loops. Science 255, 1249-1253.
8. Hedstrom, L., Farr-Jones, S., Kettner, C., and Rutter, W.J. (1994a). Converting trypsin to chymotrypsin: ground state binding does not determine substrate specificity. Biochemistry 33, 8764-8769.
9. Hedstrom L., Perona, J., and Rutter, W.J. (1994b). Converting trypsin to chymotrypsin: residue 172 is a substrate specificity determinant. Biochemistry 33, 8757-8763.
10. Kettner, C.A., Bone, R., Agard, D.A, and Bachovchin, W.W. (1988). Kinetic properties of the binding of α-lytic protease to peptide boronic acids. Biochemistry 27, 7682-7688.
11. Perona, J.J., Hsu, C.A., Craik, C.S., and Fletterick, R.J. (1993). Relocating the negative charge in the binding pocket of trypsin. J. Mol. Biol. 230, 934-949.
12. Perona, J.J., Hedstrom,L., Wagner, R.L., Rutter, W.J., Craik, C.J., and Fetterick, R.J. (1994). Exogenous acetate reconstitutes the enzymatic activity of trypsin Asp189Ser. Biochemistry 33, 3252-3259.
13. Perona, J.J., Hedstrom, L., Rutter, W.J., and Fletterick, R.J. (1995). Structural origins of substrate discrimination in trypsin and chymotrypsin, Biochemistry 34, 1489-1499.
14. Phillips, M.A, Kaplan, A.P., Rutter, W.L., and Bartlett, P.A. (1992). Transition state characterization: a new approach combining inhibitor analogues and variation in enzyme structure. Biochemistry 31, 959-963.
15. Polgar, L. (1989). Mechanisms of Protease Action (Boca Raton, USA: CRC Press, Inc.).
16. Schlechter, I., and Berger, A. (1967). On the size of the active site in proteases. I. Papain. Biochem. Biophys. Res. Commun. 27, 157-162.
17. Schellenberger, V., Turck, C.W., Hedstrom, L., and Rutter, W.J. (1993). Mapping the S1' site specificity of serine proteases using acyl transfer to mixtures of peptide nucleophiles. Biochemistry 32, 4349-4353.
18. Shotton, D.M., and Watson, H.C. (1969). Three dimensional structure of tosyl-elastase. Nature 25, 811-816.
19. Stein, R.L, Strimpler, A.M., Hori, H., and Powers, J.C. (1987). Catalysis by human leukocyte elastase: Mechanistic insights into specificity requirements. Biochemistry 26, 1301-1305.
20. Thompson, R.C., and Blout, E.R. (1973). Dependence of the kinetic parameters for elastase catalyzed amide hydrolysis on the length of peptide substrates. Biochemistry 12, 57-65.
21. Venekei, I., Szilagyi, L., Graf, L., and Rutter W.J. (1996). Attempts to convert chymotrypsin to trypsin. FEBS Letters 379, 143-147.
22. Zerner, B., Bond, R.P.M., and Bender, M.L. (1964). Kinetic evidence for the formation of acylenzyme intermediates in the α-chymotrypsin catalyzed hydrolyses of specific substrates. J. Am. Chem. Soc. 86, 3674-3679.