Abstract
AN example of two related enzymes that catalyse similar reactions but possess different active sites is provided by comparing the structure of Escherichia coli thioredoxin reductase with glutathione reductase1. Both are dimeric enzymes that catalyse the reduction of disulphides by pyridine nucleotides through an enzyme disulphide and a flavin2 . Human glutathione reductase contains four structural domains within each molecule: the flavin–adenine dinucleotide (FAD)- and nicotinamide–adenine dinucleotide phosphate (NADPH)-binding domains, the 'central' domain and the C-terminal domain that provides the dimer interface and part of the active site3,4. Although both enzymes share the same catalytic mechanism and similar tertiary structures, their active sites do not resemble each other5,6. We have determined the crystal structure of E. coli thioredoxin reductase at 2 Å resolution, and show that thioredoxin reductase lacks the domain that provides the dimer interface in glutathione reductase, and forms a completely different dimeric structure. The catalytically active disulphides are located in different domains on opposite sides of the flavin ring system. This suggests that these enzymes diverged from an ancestral nucleotide-binding protein and acquired their disulphide reductase activities independently.
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References
Karplus, P. A. & Schulz, G. E. J. molec. Biol. 195, 701–729 (1987).
Williams, C. H. Jr The Enzymes 3rd edn 13, 89–173 (1976).
Schirmer, R. H. & Schulz, G. E. in Pyridine Nucleotide Coenzymes Part B (Coenzymes and Cofactors) Vol. 2 (eds Dolphin, D., Poulson, R. & Avramovic, O. 333–379 (Wiley New York, 1987).
Thieme, R., Pai, E. F., Schirmer, R. H. & Schulz, G. E. J. molec. Biol. 152, 763–782 (1981).
Russel, M. & Model, P. J. biol. Chem. 263, 9015–9019 (1988).
Williams, C. H., Jr., Prongay, A. J., Lennon, B. W. & Kuriyan, J., in Flavins and Flavoproteins (eds Curti, B., Zannetti, G. & Ronchi, S.) (de Gruyter, Berlin, in the press).
Holmgren, A. J. biol. Chem. 264, 13963–13966 (1989).
Chothia, C. & Lesk, A. M. EMBO J. 5, 823–826 (1986).
Rossmann, M. G., A., Liljas, C. I., Bränden & Benaszak, L. J. in The Enzymes (ed. Boyer. P. D.) 61–102 (Academic, New York, 1975).
Schulz, G. E. J. molec. Biol. 145, 335–347 (1980).
Wierenga, R. K., Drenth, J. & Schulz, G. E. J. molec. Biol. 167, 725–739 (1983).
O'Donnell, M. E. & Williams, C. H. Jr Biochemistry 24, 7617–7621 (1985).
Karplus, P. A. & Schulz, G. E. J. molec. Biol. 210, 163–180 (1989).
O'Donnell, M. E. & Williams, C. H. Jr J. biol. Chem. 258, 13795–13805 (1983).
Royer, W. E. J., Hendrickson, W. A. & Chiancone, E. Science 249, 518–521 (1990).
Prongay, A. J., Engelke, D. R. & Williams, C. H. Jr J. biol. Chem. 264, 2656–2664 (1989).
Kuriyan, J., Wong, L., Russel, M. & Model, P. J. biol. Chem. 264, 12752–12753 (1989).
Terwilliger, T. C. & Eisenberg, D. Acta crystallogr. A39, 813–817 (1983).
Wang, B. C. Meth. Enzym. 115, 90–112 (1985).
Brünger, A. T., Kuriyan, J. & Karplus, M. Science 235, 458–460 (1987).
Brünger, A. T. X-PLOR (Version 1.5) Manual (The Howard Hughes Medical Institute and Department of Molecular Biophysics and Biochemistry, Yale University, Connecticut, 1988).
Jones, T. A. & Thirup, S. EMBO J. 5, 819–822 (1986).
Ramachandran, G. N. & Sasisekharan, V. Adv. Protein Chem. 23, 283–437 (1968).
Kabsch, W. & Sander, C. Biopolymers 22, 2577–2637 (1983).
Priestle, J. P. J. appl. Crystallogr. 21, 572–576 (1988).
Lee, B. K. & Richards, F. M. J. molec. Biol. 55, 379–400 (1971).
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Kuriyan, J., Krishna, T., Wong, L. et al. Convergent evolution of similar function in two structurally divergent enzymes. Nature 352, 172–174 (1991). https://doi.org/10.1038/352172a0
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DOI: https://doi.org/10.1038/352172a0
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