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Do you know? What secrets are hidden in the diversity of the GST family?
Did you know? Glutathione S-transferases (GSTs) are a very important enzyme family in organisms. Their diversity and functions mean that our understanding of these enzymes is still incomplete. The main role of GSTs in cells is to promote the detoxification of poisons. They can catalyze the combination of glutathione (GSH) with various exogenous substances, making these substances more suitable for excretion from the body.
The GST family currently includes three superfamilies: cytoplasmic, mitochondrial, and microplasmic membrane proteins (MAPEG), and they show great diversity in amino acid sequences.
Variations in the structure and function of GST mean that the function of many sequences in public databases remains unknown. In fact, according to the latest research, GSTs can even account for up to 10% of the cytoplasmic proteins in some mammalian organs.
GST classification and naming
Based on protein sequence and structure, GSTs are further classified into multiple categories of cytoplasmic, mitochondrial, and MAPEG superfamilies. For example, cytoplasmic GST is divided into 13 categories based on its structure, while mitochondrial GST belongs to the kappa category. This classification is not only based on sequence similarity but also on their respective functions and roles.
Early GST nomenclature called them "Y" proteins because during chromatographic separation they fell into the "Y" fraction.
The current nomenclature is to use a lowercase letter to indicate the species (for example, "h" for human), followed by the abbreviation of GST, an uppercase category designation, and finally Arabic numerals to indicate the subfamily. This labeling method helps scientists better identify and study different GST subtypes.
Structure and function of GST
The structure of GST includes a glutathione binding site, which is a key active region responsible for catalyzing the binding of GSH to exogenous substances. Most mammalian GSTs exist as dimers, a structure that enables them to efficiently catalyze reactions with different substrates.
Research shows that the diversity of the GST family may be related to its adaptation to natural toxins in the environment, allowing it to play an important role in chemical metabolism and cell signaling pathways.
The role of GST in cell signaling
In addition to their main detoxification function, GSTs can also bind to non-substrate ligands, which is of great significance in cell signaling. For example, some GST isoenzymes can inhibit kinase functions related to cell proliferation and death. The regulation of these small molecules may affect the life and death of cells, thereby changing the development of cancer and drug resistance.
The link between GST and cancer
More and more evidence shows that GST, especially GSTP, is closely related to cancer development and chemotherapy resistance. The overexpression of GSTP in many cancers has led scientists to realize that in addition to participating in detoxification reactions, it may also play other physiological roles in tumor cells.
High levels of GST may be directly related to cell resistance to chemotherapy drugs, making GST a hot topic in cancer research.
Clinical significance of GST
GST is associated with a variety of diseases not just in cancer. For example, GST variations may affect an individual's sensitivity to disease, especially in some respiratory and cardiovascular diseases, where the manifestations of GST are closely related to pathophysiological changes. They may also serve as biomarkers for monitoring tissue damage.
GST-tags and applications
In the field of biotechnology, GST can be used in protein purification processes, and target proteins can be effectively separated through GST tags and GST-pull-down experiments. This not only enhances protein acquisition efficiency, but also provides a deeper understanding of the interactions between proteins.
Such a diverse GST family contains countless secrets. Perhaps they will help us solve the mysteries of how to overcome major challenges such as cancer in future scientific research. Do you want to know what the GST family can also reveal about human biology? What are the mysteries?
