75 by: Emily Fagg
Student – Emily Fagg
Enzyme: Tryptophan synthase
E.C. number: 4.2.1.20
Where is enzyme found? Tryptophan synthase (TrpS) is found in fungi, bacteria, and plants (Michalska et al., 2019). It is not found in humans as humans cannot synthesize tryptophan on their own. Human’s must get tryptophan from their diet, which is why Trp is one of nine essential amino acids in humans.
What does the enzyme do? TrpS is an enzyme that helps carry out the final two reactions in the process of making Ltryptophan. It catalyzes the reaction from L-serine and indole-3-glycerol phosphate to Ltryptophan. TrpS is made up of made up of two subunits: alpha (α) and beta (β), each with distinct roles in the biosynthesis of tryptophan (Dunn et al. 2008). TrpB uses a molecule called pyridoxal phosphate (PLP) as a cofactor for the beta-substitution of the side chain of serine for an indole group, resulting in the production of tryptophan. Without tryptophan synthase, organisms would not be able to produce L-tryptophan, an essential amino acid needed for protein synthesis and other biological functions.
Any other interesting facts or important information on your enzyme? Tryptophan synthase (TrpS) is a unique enzyme that performs two different reactions simultaneously at separate active sites located on its alpha and beta subunits, making it highly efficient (Buller, 2016). TrpS plays a crucial role in the replication of Mycobacterium tuberculosis, the pathogen responsible for tuberculosis, and there is growing evidence that inhibiting this enzyme could lead to new treatments for the disease (Teixeira et al., 2020). Research suggests that drugs targeting bacterial tryptophan biosynthesis could form a new class of antibiotics, as TrpS is essential for bacterial survival in vivo (Bosken et al., 2021). Additionally, tryptophan, the product of TrpS, is a precursor to serotonin, linking this enzyme to mood regulation and brain function (Zuraikat et al., 2021).
References
Bosken, Y. K., Ai, R., Hilario, E., Ghosh, R. K., Dunn, M. F., Kan, S., Niks, D., Zhou, H., Ma, W., Mueller, L. J., Fan, L., & Chang, C. A. (2021). Discovery of antimicrobial agent
targeting tryptophan synthase. Protein Science, 31(2), 432–442. https://doi.org/10.1002/pro.4236
Buller, A. R., van Roye, P., Murciano-Calles, J., & Arnold, F. H. (2016). Tryptophan synthase uses an atypical mechanism to achieve substrate specificity. Biochemistry, 55(51), 7043–
7046. https://doi.org/10.1021/acs.biochem.6b01127
Dunn, M. F., Niks, D., Ngo, H., Barends, T. R. M., & Schlichting, I. (2008). Tryptophan synthase: The workings of a channeling nanomachine. Trends in Biochemical Sciences,
33(6), 254–264. https://doi.org/10.1016/j.tibs.2008.04.008
D’Amico, R. N., & Boehr, D. D. (2023). Allostery, engineering and inhibition of tryptophan synthase. Current Opinion in Structural Biology, 82, 102657.
https://doi.org/10.1016/j.sbi.2023.102657
Michalska, K., Gale, J., Joachimiak, G., Chang, C., Hatzos-Skintges, C., Nocek, B., Johnston, S. E., Bigelow, L., Bajrami, B., Jedrzejczak, R. P., Wellington, S., Hung, D. T., Nag, P. P.,
Fisher, S. L., Endres, M., & Joachimiak, A. (2019). Conservation of the structure and function of bacterial tryptophan synthases. IUCrJ, 6(4), 649–664.
https://doi.org/10.1107/s2052252519005955
Palmer, T., & Bonner, P. L. (2011). Monomeric and oligomeric enzymes. Enzymes, 2, 76–83. https://doi.org/10.1533/9780857099921.1.76
Teixeira, C. S., Ramos, M. J., Sousa, S. F., & Cerqueira, N. M. (2019). Solving the catalytic mechanism of tryptophan synthase: An emergent drug target in the treatment of
tuberculosis. ChemCatChem, 12(1), 227–237. https://doi.org/10.1002/cctc.201901505
Zuraikat, F. M., Wood, R. A., Barragán, R., & St-Onge, M.-P. (2021, October 11). Sleep and diet: Mounting evidence of a cyclical relationship. Annual review of nutrition. doi: 10.1146/annurev-nutr-120420-021719
