Dephosphorylation

Dephosphorylation is the removal of a phosphate (PO43−) group from an organic compound by hydrolysis. It is a reversible post-translational modification. Dephosphorylation and its counterpart, phosphorylation, activate and deactivate enzymes by detaching or attaching phosphoric esters and anhydrides. A notable occurrence of dephosphorylation is the conversion of ATP to ADP and inorganic phosphate. Dephosphorylation is the removal of a phosphate (PO43−) group from an organic compound by hydrolysis. It is a reversible post-translational modification. Dephosphorylation and its counterpart, phosphorylation, activate and deactivate enzymes by detaching or attaching phosphoric esters and anhydrides. A notable occurrence of dephosphorylation is the conversion of ATP to ADP and inorganic phosphate. Dephosphorylation employs a type of hydrolytic enzyme, or hydrolase, which cleave ester bonds. The prominent hydrolase subclass used in dephosphorylation is phosphatase. Phosphatase removes phosphate groups by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl (-OH) group. The reversible phosphorylation-dephosphorylation reaction occurs in every physiological process, making proper function of protein phosphatases necessary for organism viability. Because protein dephosphorylation is a key process involved in cell signalling, protein phosphatases are implicated in conditions such as cardiac disease, diabetes, and Alzheimer's disease. The discovery of dephosphorylation came from a series of experiments examining the enzyme phosphorylase isolated from rabbit skeletal muscle. In 1955, Edwin Krebs and Edmond Fischer used radiolabeled ATP to determine that phosphate is added to the serine residue of phosphorylase to convert it from its b to a form via phosphorylation. Subsequently, Krebs and Fischer showed that this phosphorylation is part of a kinase cascade. Finally, after purifying the phosphorylated form of the enzyme, phosphorylase a, from rabbit liver, ion exchange chromatography was used to identify phosphoprotein phosphatase I and II. Since the discovery of these dephosphorylating proteins, the reversible nature of phosphorylation and dephosphorylation has been associated with a broad range of functional proteins, primarily enzymatic, but also including nonenzymatic proteins. Edwin Krebs and Edmond Fischer won the 1992 Nobel Prize in Physiology or Medicine for the discovery of reversible protein phosphorylation. Phosphorylation and dephosphorylation of hydroxyl groups belonging to neutral but polar amino acids such as serine, threonine, and tyrosine within specific target proteins is a fundamental part of the regulation of every physiologic process. Phosphorylation involves the covalent modification of the hydroxyl with a phosphate group through the nucleophilic attack of the alpha phosphate in ATP by the oxygen in the hydroxyl. Dephosphorylation involves removal of the phosphate group through a hydration reaction by addition of a molecule of water and release of the original phosphate group, regenerating the hydroxyl. Both processes are reversible and either mechanism can be used to activate or deactivate a protein. Phosphorylation of a protein produces many biochemical effects, such as changing its conformation to alter its binding to a specific ligand to increase or reduce its activity. Phosphorylation and dephosphorylation can be used on all types of substrates, such as structural proteins, enzymes, membrane channels, signaling molecules, and other kinases and phosphatases. The sum of these processes is referred to as phosphoregulation. The deregulation of phosphorylation can lead to disease. During the synthesis of proteins, polypeptide chains, which are created by ribosomes translating mRNA, must be processed before assuming a mature conformation. The dephosphorylation of proteins is a mechanism for modifying behavior of a protein, often by activating or inactivating an enzyme. Components of the protein synthetic apparatus also undergo phosphorylation and dephosphorylation and thus regulate the rates of protein synthesis.