Kinase is an enzyme that catalyzes the transfer of a phosphate group from a high energy phosphate molecule to specific substrate, such as ATP. This process is called phosphorylation, in which the substrate acquires a phosphate group and the high energy molecule contributes to the phosphate group. This process produces a phosphorylated substrate and ADP. Conversely, there are also methods by which these phosphorylated substrates remove phosphate groups to produce dephosphorylated substrates and ATP high energy molecules. When the phosphorylated substrate is given a phosphate group and ADP obtains a phosphate groups, it is called dephosphorylation. Kinases are part of a larger family of phosphotransferases. The phosphorylation state of a molecule can affect its activity, reactivity, and its ability to bind other molecules. Therefore, kinases are important in metabolism, cell signaling, protein regulation, cell trafficking, secretion processes, and many other cellular pathways, making them important for human physiology. There are many protein kinases, and according to the kinds of amino acid residues whose substrate proteins are phosphorylated, they can be divided into five categories:
1 Serine/threonine (Ser/Thr) protein kinase: the hydroxyl group of the protein is phosphorylated;
2 Tyrosine (Tyr) protein kinase: the phenolic hydroxyl group of the protein as a phosphorus receptor;
3 Histidine protein kinase: the basic group of histidine, arginine or lysine of the protein is phosphorylated, mainly in the "two-component signal system";
4 Tryptophan protein kinase: the tryptophan residue of the protein as a phosphorus receptor;
5 Aspartyl/glutamyl protein kinase: The acyl group of the protein is a phosphorus acceptor.
Protein kinases are an important class of intracellular enzymes that play a key role in most signal transduction cascades, from controlling cell growth and proliferation to the initiation and regulation of immune responses. Protein kinases, also known as phosphotransferases, phosphorylate target proteins in cells by covalently linking the phosphate to the side chain of a serine, threonine or tyrosine residue. It has subsequently been shown that kinases play an important role in the first step of intracellular immune cell signaling. For example, kinases are associated with intracellular components of receptors on the cell surface of T and B lymphocytes, and once these receptors bind to their extracellular ligands, intracellular signal cascades within these cells are initiated. Since protein kinases have been identified as a fundamental driver of inflammatory cell signaling, they have been investigated as therapeutic targets for a variety of diseases.
Because protein kinases have profound effects on cells, their activity is highly regulated. Initiate or shut down kinases by phosphorylation (sometimes by kinase itself - cis-phosphorylation/autophosphorylation), by activation of proteins or by inhibition of binding of proteins or small molecules, or by controlling their position in the cell relative to their substrate.
The catalytic subunits of many protein kinases are highly conserved and several structures have been resolved. Eukaryotic protein kinases are enzymes belonging to a very broad family of proteins that share a conserved catalytic core. There are many conserved regions in the catalytic domain of protein kinases. At the N-terminus of the catalytic domain, a glycine-rich residue segment is present near the lysine amino acid, which has been shown to be involved in ATP binding. In the central portion of the catalytic domain, there is a conserved aspartic acid which is important for the catalytic activity of the enzyme.
1. H. Patterson.; et al. Protein kinase inhibitors in the treatment of inflammatory and autoimmune diseases. Clinical and experimental immunology. 2013, 176: 1-10.
2. John E. Burke.; et al. Structural Basis for Regulation of Phosphoinositide Kinases and Their Involvement in Human Disease. Molecular Cell. 2018, 71: 653-673.