The relative ease of RNA hydrolysis is an effect of the presence of the 2' hydroxyl group.Ī phosphodiesterase is an enzyme that catalyzes the hydrolysis of phosphodiester bonds, for instance a bond in a molecule of cyclic AMP or cyclic GMP.Īn enzyme that plays an important role in the repair of oxidative DNA damage is the 3'-phosphodiesterase.ĭuring the replication of DNA, there is a hole between the phosphates in the backbone left by DNA polymerase I. The phosphodiester linkage between two ribonucleotides can be broken by alkaline hydrolysis, whereas the linkage between two deoxyribonucleotides is more stable under these conditions. Hydrolysis of phosphodiester bonds is catalyzed by phosphodiesterases, which are involved in repairing DNA sequences. In order for the phosphodiester bond to be formed and the nucleotides to be joined, the tri-phosphate or di-phosphate forms of the nucleotide building blocks are broken apart to give off energy required to drive the enzyme-catalyzed reaction. The negative charge attracts histones, metal cations such as magnesium, and polyamines. Repulsion between these negative charges influences the conformation of the polynucleic acids. Phosphodiesters are negatively charged at pH 7. These saccharide groups are derived from deoxyribose in DNA and ribose in RNA. Specifically, the phosphodiester bond links the 3' carbon atom of one sugar molecule and the 5' carbon atom of another (hence the name, 3', 5' phosphodiester linkage ). The 3' carbon of one sugar is bonded to the 5' phosphate of the adjacent sugar. The phosphate is attached to the 5' carbon. Phosphodiester bonds make up the backbones of DNA and RNA. Discussion of phosphodiesters is dominated by their prevalence in DNA and RNA, but phosphodiesters occur in other biomolecules, e.g. The "bond" involves this linkage C−O−PO − 2O−C. In chemistry, a phosphodiester bond occurs when exactly two of the hydroxyl groups ( −OH) in phosphoric acid react with hydroxyl groups on other molecules to form two ester bonds. The 5' end has a 5' carbon attached to a phosphate, and the other end, the 3' end, has a 3' carbon attached to a hydroxyl group. (Note: Those targets often need to modified in multiple locations - for example at least two ribosomal proteins are targets of ERK, one on two different amino acids.–O– linkage between phosphoric acid and two other compounds Diagram of phosphodiester bonds ( PO 3− 4) between three nucleotides. This would take a very long time if only a few ERK molecules were activated! In addition, there are 244 known direct targets identified for ERK in humans§, so even if you only had a few of each of those molecules amplification would still be needed to get a timely response! One response a cell needs to divide is an increased rate of protein synthesis, so maybe at the end of the pathway ERK needs to phosphorylate the (up to) 10 million ribosomes to increase their activity. Why questions are typically difficult in biology, but I'll give a slightly hypothetical example of why this is important. For instance, if each time a RAF molecule gets activated it phosphorylates 20 molecules of MEK, then you've amplified the signal by 20 times. Many if not all of the steps described in this article can amplify a signal.įor example each step in the section titled Phosphorylation example: MAPK signaling cascade involves a kinase phosphorylating downstream molecules. There is a sketch of DNA below the phosphorylated c-Myc and an arrow pointing from the DNA with the caption Transcription of genes promoting cell growth and division. One end of the arrow points to the caption Phosphorylation of other transcription factors, and the other end of the arrow points to a curved arrow between an oval labeled c-Myc and a second oval labeled c-Myc with a phosphate attached. The second arrow points into the nucleus and once inside the nucleus the arrow splits. One arrow points to the caption Phosphorylation of cytosolic targets promoting growth and division. From the phosphorylated ERK there are 2 arrows. Below the phosphorylated MEK is an oval labeled ERK with an arrow pointing to an oval with the label ERK with a phosphate attached and the caption MAP kinase,MAPK next to it. Below the Raf an oval with the label MEK has a curved arrow pointing to an oval with the label MEK and a phosphate attached, with the caption MAPK kinase, MKK next to it. Inside the plasma membrane arrows point from the epidermal growth factor receptor towards a structure labeled Raf with the caption MAPK kinase kinase, MKKK next to the Raf structure. 2 blue circles are attached to the epidermal growth factor located within the plasma membrane. Epidermal growth factor is shown as small blue circles outside of the plasma membrane.
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