Abstract
A model is proposed for the structure of an inhibited derivative of an enzyme which hydrolyses proteins. It is based on a map of the electron density distribution at 2 Å resolution and interpreted in terms of a previously reported sequence of 241 amino-acids. The map has been derived from a Fourier synthesis of 24,500 terms and represents two crystallographically independent molecules, each of molecular weight 25,000, which are nearly identical in their tertiary structure. The enzyme is composed almost entirely of extended polypeptide chains. A chemical marker unambiguously defines the position of the active centre. The position and orientation of the residues known to be important in catalysis are clearly seen. The mechanism by which the inactive precursor is converted into an active enzyme is revealed.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Blow, D. M., Rossmann, M. G., and Jeffery, B. A., J. Mol. Biol., 8, 65 (1964).
Sigler, P. B., Jeffery, B. A., Matthews, B. W., and Blow, D. M., J. Mol. Biol., 15, 175 (1966).
Matthews, B. W., Acta Cryst., 20, 230 (1966).
Hartley, B. S., Nature, 201, 1284 (1964).
Hartley, B. S., in The Structure and Activity of Enzymes (edit. by Goodwin, T. W., Harris, J. I., and Hartley, B. S.), 47 (Academic Press, London, 1964).
Hartley, B. S., and Kauffman, D. L., Biochem. J., 101, 229 (1966).
Keil, B., Šorm, F., and Prusík, Z., Biophys. Biochim. Acta, 78, 559 (1963).
Meloun, B., Kluh, I., Kostka, V., Morávek, L., Prusíkz, Z., Vaněček, J., Keil, B., and Šorm, F., Biophys. Biochim. Acta, 130, 543 (1966).
Bernal, J. D., Fankuchen, I., and Perutz, M. F., Nature, 141, 523 (1938).
Sigler, P. B., and Blow, D. M., J. Mol. Biol., 14, 640 (1965).
Rossmann, M. G., Acta Cryst., 13, 221 (1960).
Lundberg, B., Acta Cryst., 18, 576 (1965).
Diamond, R., Acta Cryst., 11, 129 (1958).
Diamond, R., Acta Cryst., 21, 253 (1966).
Dickerson, R. E., Kendrew, J. C., and Strandberg, B. E., in Computing Methods and the Phase Problem in X-ray Crystal Analysis (edit. by R. Pepinsky), 248 (Pergamon, Oxford, 1961).
Blow, D. M., and Crick, F. H. C., Acta Cryst., 12, 794 (1959).
Matthews, B. W., Acta Cryst., 20, 82 (1966).
Gossling, T. H., Acta Cryst., 22, 465 (1967).
Desnuelle, P., The Enzymes (edit. by Boyer, P. D., Lardy, H., and Myrbäck, K.), 4, 93 (Academic Press, New York, 1960).
Kallos, J., and Rizok, D., J. Mol. Biol., 9, 255 (1964).
Phillips, D. C., Proc. U.S. Nat. Acad. Sci, 57, 484 (1967).
Kendrew, J. C., Watson, H. C., Strandberg, B. E., Dickerson, R. E., Phillips, D. C., and Shore, V. C., Nature, 190, 666 (1961).
Blake, C. C. F., Koenig, D. F., Mair, G. A., North, A. C. T., Phillips, D. C., and Sarma, V. R., Nature, 206, 757 (1965).
Kartha, G., Bello, J., and Harker, D., Nature, 213, 862 (1967).
For a recent review see Cunningham, L., in Comprehensive Biochemistry (edit. by Florkin, M., and Stotz, E. H.), 16, 85 (Elsevier, Amsterdam, 1965).
Bender, M. L., and Kézdy, F. J., J. Amer. Chem. Soc., 86, 3704 (1964).
Oppenheimer, H. L., Labouesse, B., and Hess, G. P., J. Biol. Chem., 241, 2720 (1966).
Keizer, J., and Bernhard, S. A., Biochemistry, 5, 4127 (1966).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
MATTHEWS, B., SIGLER, P., HENDERSON, R. et al. Three-dimensional Structure of Tosyl-α-chymotrypsin. Nature 214, 652–656 (1967). https://doi.org/10.1038/214652a0
Received:
Issue Date:
DOI: https://doi.org/10.1038/214652a0
This article is cited by
-
Serine protease dynamics revealed by NMR analysis of the thrombin-thrombomodulin complex
Scientific Reports (2021)
-
Fragment-based discovery of the first nonpeptidyl inhibitor of an S46 family peptidase
Scientific Reports (2019)
-
Structural and mutational analyses of dipeptidyl peptidase 11 from Porphyromonas gingivalis reveal the molecular basis for strict substrate specificity
Scientific Reports (2015)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.