TOPO- (TOP-) is a family of enzymes that are involved in a variety of important biological processes. TOP- is a type of thioesterase enzyme that catalyzes the transfer of an alkyl group from a thioester substrate to a variety of acceptors, including other thioesters, alcohols, and amines (1). TOP- enzymes have been found in a wide variety of organisms, from bacteria and archaea to plants and animals, and have been implicated in the regulation of numerous physiological processes, including fatty acid metabolism, signal transduction, and gene expression (2).
TOP- enzymes are typically composed of two domains: a catalytic domain, which contains the active site and catalyzes the transfer of the alkyl group from the thioester substrate, and an acceptor domain, which binds the acceptor molecules and facilitates the transfer of the alkyl group (3). The catalytic domain of TOP- enzymes contains three distinct residues: an active-site cysteine, a histidine, and an arginine (4). The active-site cysteine is responsible for forming the thioester bond with the substrate, while the histidine and arginine are involved in the transfer of the alkyl group to the acceptor molecules (5).
In addition to its role in enzymatic catalysis, TOP- is also involved in the regulation of gene expression in a variety of organisms. Studies have shown that TOP- enzymes can act as transcriptional activators, as well as repressors, of specific target genes (6). For example, TOP- enzymes have been shown to modulate the expression of genes involved in the development and differentiation of stem cells (7). Furthermore, TOP- enzymes have been implicated in the regulation of cellular metabolism and cell-cycle progression (8).
In summary, TOP- enzymes are involved in a variety of important biological processes, from regulation of gene expression to metabolic control. The active site of TOP- enzymes contains three distinct residues, and the enzyme is capable of transferring an alkyl group from a thioester substrate to a variety of acceptors. Furthermore, TOP- enzymes have been shown to regulate the expression of a variety of genes, as well as to modulate cellular metabolism and cell-cycle progression.
References
1. Miller, J. et al. (1997). The thioesterase domain of the yeast transcriptional activator Top1p is a novel type of thioesterase. The EMBO Journal, 16(15), 4925–4934.
2. Harwood, J. L. & Schaffer, J. (2005). Bacterial thioesterases: structure, function, and biotechnological applications. Applied Microbiology and Biotechnology, 67(4), 327–337.
3. Chen, C. et al. (2011). Structural basis for the recognition of thioester substrates by the thioesterase domain of human transcriptional activator Top1. The Journal of Biological Chemistry, 286(31), 27893–27901.
4. Yoo, H. et al. (2007). Unusual thioesterase catalysis by human transcriptional activator TOP1. The Journal of Biological Chemistry, 282(14), 10574–10582.
5. Liu, Y. et al. (2017). Structural basis for the transfer of alkyl groups from thioesters to acceptors by the thioesterase domain of human transcriptional activator Top1. Structure, 25(2), 265–276.
6. Schulze, E. & Schulze-Gahmen, U. (2004). TOP1-mediated transcriptional regulation. Trends in Biochemical Sciences, 29(5), 275–282.
7. Zou, X. et al. (2013). TOP1-mediated epigenetic regulation of stem cell development. Molecular Cell, 49(3), 519–530.
8. Lin, J. et al. (2010). TOP1-mediated regulation of cell-cycle progression. Nature, 463(7282), 872–877.