4 by: Rowan Jones
Student – Rowan Jones
Enzyme & E.C. Number: Adenosine deaminase; EC 3.5.4.4
Where is the enzyme found? Adenosine deaminase is found across bacteria, plants, mammals, and invertebrates (Cristalli et al. 2001). The amino acid structure is highly conserved across all these taxa. Adenosine deaminase is present in all cells but cells in developing T cells, the stomach and intestine, and the fetal-maternal interface (Dusing et al. 1997).
What does the enzyme do? The enzyme regulates the levels of adenosine in cells. It catalyses an elimination-addition (nearly SN2) reaction that removes the amine group from adenosine or from 2-deoxyadenosine and replaces it with a hydroxyl group in the same location. This converts the substrate into inosine and 2-deoxyinosine, respectively, and produces ammonia as a byproduct. Adenosine deaminase plays an important role in the immune system, with a lack of the enzyme being associated with severe combined immunodeficiency disease (SCID; Wilson et al. 1991). This disease often affects newborns (Hershfield 1993).
Interesting facts or important information on your enzyme – ADA-caused severe immunodeficiency disease was the first candidate for clinical gene therapy trials, because of how severe the effects of SCID are (Wilson et al. 1991). ADA is only of a family of different nucleoside deaminases, but it does not necessarily have a structure that indicates those enzymes are closely evolutionarily related (Carter 1995).
References
Antonioli, L., Colucci, R., La Motta, C., Tuccori, M., Awwad, O., Da Settimo, F., Blandizzi, C., & Fornai, M. (2012). Adenosine Deaminase in the Modulation of Immune System and its Potential as a Novel Target for Treatment of Inflammatory Disorders. Current Drug Targets, 13(6), 842–862. https://doi.org/10.2174/138945012800564095
Carter, C. W. (1995). The nucleoside deaminases for cytidine and adenosine: Structure, transition state stabilization, mechanism, and evolution. Biochimie, 77(1–2), 92–98. https://doi.org/10.1016/0300-9084(96)88110-7
Cristalli, G., Costanzi, S., Lambertucci, C., Lupidi, G., Vittori, S., Volpini, R., & Camaioni, E. (2001). Adenosine deaminase: Functional implications and different classes of inhibitors. Medicinal Research Reviews, 21(2), 105–128. https://doi.org/10.1002/1098-1128(200103)21:2<105::AID-MED1002>3.0.CO;2-U
Dusing, M. R., Brickner, A. G., Thomas, M. B., & Wiginton, D. A. (1997). Regulation of Duodenal Specific Expression of the Human Adenosine Deaminase Gene *. Journal of Biological Chemistry, 272(42), 26634–26642. https://doi.org/10.1074/jbc.272.42.26634
Garcia-Gil, M., Camici, M., Allegrini, S., Pesi, R., & Tozzi, M. G. (2021). Metabolic Aspects of Adenosine Functions in the Brain. Frontiers in Pharmacology, 12, 672182. https://doi.org/10.3389/fphar.2021.672182
Hershfield, M., & Tarrant, T. (1993). Adenosine Deaminase Deficiency. In M. P. Adam, J. Feldman, G. M. Mirzaa, R. A. Pagon, S. E. Wallace, & A. Amemiya (Eds.), GeneReviews®. University of Washington, Seattle. http://www.ncbi.nlm.nih.gov/books/NBK1483/
Kamat, S. S., Bagaria, A., Kumaran, D., Holmes-Hampton, G. P., Fan, H., Sali, A., Sauder, J. M., Burley, S. K., Lindahl, P. A., Swaminathan, S., & Raushel, F. M. (2011). Catalytic Mechanism and Three-Dimensional Structure of Adenine Deaminase,. Biochemistry, 50(11), 1917–1927. https://doi.org/10.1021/bi101788n
Luo, M., Singh, V., Taylor, E. A., & Schramm, V. L. (2007). Transition-State Variation in Human, Bovine, and Plasmodium falciparum Adenosine Deaminases. Journal of the American Chemical Society, 129(25), 8008–8017. https://doi.org/10.1021/ja072122y
National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 60961, Adenosine. Retrieved October 11, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Adenosine.
National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 135398641, Inosine. Retrieved October 11, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Inosine.
Niu, W., Shu, Q., Chen, Z., Mathews, S., Di Cera, E., & Frieden, C. (2010). The Role of Zn2+ on the Structure and Stability of Murine Adenosine Deaminase. The Journal of Physical Chemistry B, 114(49), 16156–16165. https://doi.org/10.1021/jp106041v
Wilson, D. K., Rudolph, F. B., & Quiocho, F. A. (1991). Atomic Structure of Adenosine Deaminase Complexed with a Transition-State Analog: Understanding Catalysis and Immunodeficiency Mutations. Science, 252(5010), 1278–1284.
