Simulation of the activation of α-chymotrypsin: Analysis of the pathway and role of the propeptide

Protein Science

Volumn 13, Issue 12, 2004, Pages 3139-3150

  Janka, Mátrai ^a   Verheyden, Gert ^a,b   Krüger, Peter ^a,c   Engelborghs, Yves ^a  

^a UNIVERSITY OF LEUVEN   (Belgium)

^b INNOGENETICS   (Belgium)

^c ALA Analytisches Labor GmbH   (Germany)

Author keywords

A chain (propeptide); Chymotrypsin; Chymotrypsinogen; Conformational change; Fluorescence stopped flow; Molecular dynamics simulation; Pathway calculation; Targeted molecular dynamics

Indexed keywords

AMINO ACID; CHYMOTRYPSIN A; CHYMOTRYPSINOGEN; ENZYME PRECURSOR; PROTEIN PRECURSOR;

AMINO ACID SEQUENCE; ARTICLE; CATTLE; CONFORMATIONAL TRANSITION; ENZYME ACTIVATION; ENZYME CONFORMATION; ENZYME INACTIVATION; FLUORESCENCE; MOLECULAR DYNAMICS; NONHUMAN; PH; PRIORITY JOURNAL; RAT; SIMULATION;

AMINO ACID SEQUENCE; ANIMALS; CATTLE; CHYMOTRYPSIN; COMPUTER SIMULATION; ENZYME ACTIVATION; ENZYME PRECURSORS; HYDROGEN-ION CONCENTRATION; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PROTEIN CONFORMATION; RATS; SEQUENCE ALIGNMENT; SIGNAL TRANSDUCTION; TIME FACTORS;

BOS TAURUS; BOVINAE; STAPHYLOCOCCUS PHAGE 187;

EID: 9344250538     PISSN: 09618368     EISSN: None     Source Type: Journal    
DOI: 10.1110/ps.04825004     Document Type: Article

References (33)

1. Berendsen, H.J.C., Postma, J.P.M., Van Gunsteren, W.F., and Hermans, J. 1981. Interaction models for water in relation in protein hydration. Reidel, Dordrecht. The Netherlands.
2. Berendsen, H.J.C., Postma, J.P.M., Van Gunsteren, W.F., Dinola, A., and Haak, J.R. 1984. Molecular-Dynamics with coupling to an external bath. J. Chem. Phys. 81: 3684-3690.
3. Bernstein, F.C., Koetzle, T.F., Williams, G.J.B., Meyer, E.F., Brice, M.D., Rodgers, J.R., Kennard, O., Shimanouchi, T., and Tasumi, M. 1977. Protein Data Bank: A computer-based archival file for macromolecular structures. J. Mol. Biol. 112: 535-542.
4. Blevins, R.A. and Tulinsky, A. 1985. The refinement and the structure of the dimer of α-chymotrypsin at 1.67-Å resolution. J. Biol. Chem. 260: 4264-4275.
5. Bode, W. 1979. Transition of bovine trypsinogen to a trypsin-like state upon strong ligand-binding. 2. Binding of the pancreatic trypsin-inhibitor and of isoleucine-valine and of sequentially related peptides to trypsinogen and to P-guanidinobenzoate-trypsinogen. J. Mol. Biol. 127: 357-374.
6. Bode, W., Schwager, P., and Huber, R. 1978. Transition of bovine trypsinogen to a trypsin-like state upon strong ligand binding. The refined crystal structures of the bovine trypsinogen-pancreatic trypsin inhibitor complex and of its ternary complex with Ile-Val at 1.9 Å resolution. J. Mol. Biol. 118: 99-112.
7. Cohen, G.H., Silverton, E.W., and Davies, D.R. 1981. Refined crystal structure of gamma-chymotrypsin at 1.9 Å resolution. Comparison with other pancreatic serine proteases. J. Mol. Biol. 148: 449-479.
8. Diamond, R. 1974. Real-space refinement of the structure of hen egg-white lysozyme. J. Mol. Biol. 82: 371-391.
9. Fersht, A.R. and Renard, M. 1974. pH dependence of chymotrypsin catalysis. Appendix: Substrate binding to dimeric α-chymotrypsin studied by X-ray diffraction and the equilibrium method. Biochemistry 13: 1416-1426.
10. Guex, N. and Peitsch, M.C. 1997. SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modeling. Electrophoresis 18: 2714-2723.
11. Heremans, L. and Heremans, K. 1989a. Pressure effects on the Raman-spectrum of proteins. Stability of the salt bridge in trypsin and elastase. J. Mol. Biol. 214: 305-314.
12. -. 1989b. Raman-spectroscopic study of the changes in secondary structure of chymotrypsin. Effect of pH and pressure on the salt bridge. Biochim. Biophys. Acta 999: 192-197.
13. Kardos, J., Bodi, A., Zavodszky, P., Venekei, I., and Graf, L. 1999. Disulfide-linked propeptides stabilize the structure of zymogen and mature pancreatic serine proteases. Biochemistry 38: 12248-12257.
14. Kraulis, P.J. 1991. MOLSCRIPT: A program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallogr. 24: 946-950.
15. Kruger, P. and Szameit, A. 1992. Simlys Version 2.0. Comput. Phys. Commun. 72: 265-268.
16. Kruger, P., Luke, M., and Szameit, A. 1991. Simlys - A software package for trajectory analysis of molecular-dynamics simulations. Comput. Phys. Commun. 62: 371-380.
17. Levitt, M. 1983. Molecular dynamics of native protein. 2. Analysis and nature of motion. J. Mol. Biol. 168: 621-657.
18. Sayle, R.A. and Milner-White, E.J. 1995. RASMOL: Biomolecular graphics for all. Trends Biochem. Sci. 20: 374.
19. Schlitter, J., Engels, M., Kruger, P., Jacoby, E., and Wollmer, A. 1993. Targeted molecular dynamics simulation of conformational change. Application to the T[-]R transition in insulin. Mol. Simul. 10: 291-308.
20. Schlitter, J., Engels, M., and Kruger, P. 1994. Targeted molecular dynamics. A new approach for searching pathways of conformational transitions. J. Mol. Graph. 12: 84-89.
21. Stoesz, J.D. and Lumry, R.W. 1978. Refolding transition of α-chymotrypsin, pH and salt dependence. Biochemistry 17: 3693-3699.
22. -. 1979. Effects of chemical modification on the refolding transition of α-chymotrypsin. Biophys. Chem. 10: 105-112.
23. Swegat, W., Krueger, P., and Schlitter, J. 1997. TMD. Implementation in GROMOS96, pp. 1-11.
24. Tsukada, H. and Blow, D.M. 1985. Structure of α-chymotrypsin refined at 1.68 Å resolution. J. Mol. Biol. 184: 703-711.
25. Van Gunsteren, W.F. 1996. Biomolecular simulation: The GROMOS96 manual and user guide. vdf Hochschulverlag AD an der ETH Zürich, Zurich.
26. Varallyay, V., Lengyel, Z., Graf, L., and Szilagyi, L. 1997. The role of disulfide bond C191-C220 in trypsin and chymotrypsin. Biochem.Biophys. Res. Commun. 230: 592-596.
27. Venekei, I., Szilagyi, L., Graf, L., and Rutter, W.J. 1996. Attempts to convert chymotrypsin to trypsin. FEBS Lett. 379: 143-147.
28. Verheyden, G., Volckaert, G., and Engelborghs, Y. 2000. Expression of chymotrypsin(ogen) in the thioredoxin reductase deficient mutant strain of Escherichia coli AD494(DE3) and purification via a fusion product with a hexahistidine tail. J. Chromatogr. B Biomed. Sci. Appl. 737: 213-224.
29. Verheyden, G., Mátrai, J., Volckaert, G., and Engelborghs, Y. 2004. A fluorescence stopped flow kinetic study of the conformational activation of α-chymotrypsin and several mutants. Protein Sci. 13: 2533-2540.
30. Vriend, G. 1990. WHAT IF: A molecular modeling and drug design program. J. Mol. Graph. 8: 52-56.
31. Wang, D.C., Bode, W., and Huber, R. 1985. Bovine chymotrypsinogen A X-ray crystal structure analysis and refinement of a new crystal form at 1.8 Å resolution. J. Mol. Biol. 185: 595-624.
32. Wroblowski, B., Diaz, J.F., Schulitter, J., and Engelborghs, Y. 1997. Modelling pathways of α-chymotrypsin activation and deactivation. Protein Eng. 10: 1163-1174.
33. Zagrovic, B., Snow, D.C., Shirts, R.M., and Pande, S.V. 2002. Simulation of folding of a small α-helical protein in atomistic detail using worldwide-distributed computing. J. Mol. Biol. 323: 927-937.