Abstract
MANDELATE racemase (MR) and muconate lactonizing enzyme (MLE) catalyse separate and mechanistically distinct reactions necessary for the catabolism of aromatic acids by Pseudomonas putida1–3. The X-ray crystal structure of MR, solved at 2.5 Å resolution, reveals that the secondary, tertiary and quaternary structures of MR and MLE4 are remarkably similar; also, MR and MLE are about 26% identical in primary structure5. However, MR has no detectable MLE activity and vice versa. Thus, MR and MLE constitute the first example of enzymes that catalyse different reactions, as opposed to mechanistically identical reactions on different substrates, yet possess sufficient structural and sequence identity that they are likely to have evolved from a common ancestor. The discovery that MR and MLE catalyse different reactions but share a common structural framework has broad implications for the natural evolution of enzymes and metabolic pathways, as well as for the rational modification of enzyme activities.
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
Halpin, R. A., Hegeman, G. D. & Kenyon, G. L. Biochemistry 20, 1525–1533 (1981).
Hegeman, G. D. J. Bact. 91, 1140–1154 (1966).
Ornston, L. N. J. biol. Chem. 241, 3800–3810 (1966).
Goldman, A., Ollis, D. L. & Steitz, T. A. J. molec. Biol. 194, 143–153 (1987).
Tsou, A. Y. et al. Biochemistry (in the press).
Stenkamp, R. E. & Jensen, L. H. In Structural Aspects of Recognition and Assembly in Biological Molecules (eds Balaban, M., Sussman. J. L, Traub, W. & Yonath, A.) (Balaban ISS, Philadelphia, 1981).
Lindqvist, Y. & Brändén, C.-L. Proc. natn. Acad. Sci. U.S.A. 82, 6855–6859 (1985).
Banner, D. W. et al. Nature 255, 609–614 (1975).
Farber, G. K. & Petsko, G. A. Trends biochem. Sci. 15, 228–234 (1990).
Rossmann, M. J. & Argos, P. J. biol. Chem. 250, 7525–7532 (1975).
Greer, J. J. molec. Biol. 153, 1027–1042 (1981).
Schultz, G. E. & Schirmer, R. H. Principles of Protein Structure (Springer, New York, 1979).
Chothia, C. & Lesk, A. M. EMBO J. 5, 823–826 (1986).
Schultz, G. E. Angew. Chem. int. Ed. Engl. 20, 143–151 (1981).
Lin, D. T. et al. J. Am. chem. Soc. 110, 323–324 (1988).
Ngai, K.-L. & Kallen, R. G. Biochemistry 22, 5231–5236 (1983).
Tsou, A. Y., Ransom, S. C., Gerlt, J. A., Powers, V. M. & Kenyon, G. L. Biochemistry 28, 969–975 (1989).
Neidhart, D. J. et al. J. biol. Chem. 263, 9268–9270 (1988).
O'Halloran, T. V., Lippard, S. J., Richmond, T. J. & Klug, A. J. molec. Biol. 194, 705–712 (1987).
Wang, B. C. Meth. Enzym. 115, 90–111 (1985).
Brünger, A. T., Kuriyan, J. & Karplus, M. Science 235, 458–460 (1987).
Hendrickson, W. A. & Konnert, J. H. in Biomolecular Structure, Function, Conformation and Evolution (ed. Srinivasan, R.) Vol. 1 43–57 (Pergamon, Oxford, 1980).
Terwilliger, T. C. & Eisenberg, D. Acta. crystallogr. A39, 813–817 (1983).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Neidhart, D., Kenyon, G., Gerlt, J. et al. Mandelate racemase and muconate lactonizing enzyme are mechanistically distinct and structurally homologous. Nature 347, 692–694 (1990). https://doi.org/10.1038/347692a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/347692a0
This article is cited by
-
Identification and characterization of 3,6-anhydro-L-galactonate cycloisomerase belonging to theenolase superfamily
Biotechnology and Bioprocess Engineering (2015)
-
Evolutionary biochemistry: revealing the historical and physical causes of protein properties
Nature Reviews Genetics (2013)
-
Assignment of protein function in the postgenomic era
Nature Chemical Biology (2005)
-
Directed evolution of new catalytic activity using the α/β-barrel scaffold
Nature (2000)
-
Crystal structure of asparagine synthetase reveals a close evolutionary relationship to class II aminoacyl-tRNA synthetase
Nature Structural Biology (1998)
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.
