The phosphodiester bonds are covalent bonds that occur between two of the oxygen atoms of a phosphate group and hydroxyl groups of two different molecules. In this type of bond, the phosphate group acts as a stable bonding "bridge" between the two molecules through their oxygen atoms.
The fundamental role of phosphodiester bonds in nature is that of the formation of nucleic acid chains, both DNA and RNA. Together with the pentose sugars (deoxyribose or ribose, as the case may be), the phosphate groups are part of the supporting structure of these important biomolecules.
Phosphodiester bond in the DNA skeleton (Source: File: Phosphodiester bond.png, File: PhosphodiesterBondDiagram.png: User: G3pro (talk) User: G3pro at en.wikipedia.org Derivative work: User: Merops (talk) Derivative work: User: Deneapol (talk) Derivative work: User: KES47 (talk) Text tweaks: Incnis Mrsi (talk) Text tweaks: DMacks (talk)) Derivative work: User: Miguelferig (talk) with ionization, via Wikimedia Commons)
The nucleotide chains of DNA or RNA, like proteins, can assume different three-dimensional conformations that are stabilized by non-covalent bonds, such as hydrogen bonds between complementary bases.
However, the primary structure is given by the linear sequence of nucleotides covalently linked via phosphodiester bonds.
How is a phosphodiester bond formed?
Like peptide bonds in proteins and glycosidic bonds between monosaccharides, phosphodiester bonds result from dehydration reactions in which a water molecule is lost. Here is the general scheme of one of these dehydration reactions:
HX 1 -OH + HX 2 -OH → HX 1 -X 2 -OH + H 2 O
Phosphate ions correspond to the completely deprotonated conjugate base of phosphoric acid and are called inorganic phosphates, whose abbreviation is denoted as Pi. When two phosphate groups are linked together, an anhydrous phosphate bond forms, and a molecule known as inorganic pyrophosphate or PPi is obtained.
When a phosphate ion is attached to a carbon atom in an organic molecule, the chemical bond is called a phosphate ester, and the resulting species is an organic monophosphate. If the organic molecule binds to more than one phosphate group, organic diphosphates or triphosphates are formed.
When a single inorganic phosphate molecule is attached to two organic groups, a phosphodiester or "phosphate diester" bond is employed. It is important not to confuse phosphodiester bonds with high-energy phosphoanhydro bonds between the phosphate groups of molecules like ATP, for example.
Differences between phosphates and phosphoryls (Source: Strater, via Wikimedia Commons)
The phosphodiester linkages between adjacent nucleotides consist of two phosphoester linkages that occur between the hydroxyl at the 5 'position of one nucleotide and the hydroxyl at the 3' position of the next nucleotide in a DNA or RNA strand.
Depending on the conditions of the environment, these bonds can be hydrolyzed both enzymatically and non-enzymatically.
Enzymes involved
The formation and breaking of chemical bonds is crucial to all vital processes as we know them, and the case of phosphodiester bonds is no exception.
Among the most important enzymes that can form these bonds are DNA or RNA polymerases and ribozymes. Phosphodiesterase enzymes are capable of enzymatically hydrolyzing them.
During replication, a crucial process for cell proliferation, in each reaction cycle a dNTP (deoxynucleotide triphosphate) complementary to the template base is incorporated into the DNA through a nucleotide transfer reaction.
The polymerase is responsible for forming a new bond between the 3'-OH of the template strand and the α-phosphate of the dNTP, thanks to the energy released from the breaking of the bonds between the α and β phosphates of the dNTP, which are linked by phosphoanhydro bonds.
The result is the extension of the chain by one nucleotide and the release of a molecule of pyrophosphate (PPi) s. It has been determined that these reactions merit two divalent magnesium ions (Mg 2+), the presence of which allows the electrostatic stabilization of the nucleophile OH - to achieve the approach towards the active site of the enzyme.
The pK a of a phosphodiester bond is close to 0, so in an aqueous solution these bonds are completely ionized, negatively charged.
This gives nucleic acid molecules a negative charge, which is neutralized thanks to ionic interactions with the positive charges of protein amino acid residues, electrostatic bonding with metal ions, or association with polyamines.
In an aqueous solution the phosphodiester bonds in DNA molecules are much more stable than in RNA molecules. In an alkaline solution, these bonds in RNA molecules are cleaved by intramolecular displacement of the nucleoside at the 5 'end by a 2' oxyanion.
Function and examples
As mentioned, the most relevant role of these bonds is their participation in the formation of the backbone of nucleic acid molecules, which are one of the most important molecules in the cellular world.
The activity of topoisomerase enzymes, which actively participate in DNA replication and protein synthesis, depends on the interaction of the phosphodiester bonds at the 5 'end of DNA with the side chain of tyrosine residues in the active site of these enzymes.
Molecules that participate as second messengers, such as cyclic adenosine monophosphate (cAMP) or cyclic guanosine triphosphate (cGTP), possess phosphodiester bonds that are hydrolyzed by specific enzymes known as phosphodiesterases, whose participation is of utmost importance for many signaling processes cellular.
Glycerophospholipids, fundamental components in biological membranes, are composed of a glycerol molecule that is attached via phosphodiester bonds to the polar "head" groups that constitute the hydrophilic region of the molecule.
References
- Fothergill, M., Goodman, MF, Petruska, J., & Warshel, A. (1995). Structure-Energy Analysis of the Role of Metal Ions in Phosphodiester Bond Hydrolysis by DNA Polymerase I. Journal of the American Chemical Society, 117 (47), 11619-11627.
- Lodish, H., Berk, A., Kaiser, CA, Krieger, M., Bretscher, A., Ploegh, H., Martin, K. (2003). Molecular Cell Biology (5th ed.). Freeman, WH & Company.
- Nakamura, T., Zhao, Y., Yamagata, Y., Hua, YJ, & Yang, W. (2012). Watching DNA polymerase η make a phosphodiester bond. Nature, 487 (7406), 196-201.
- Nelson, DL, & Cox, MM (2009). Lehninger Principles of Biochemistry. Omega Editions (5th ed.)
- Oivanen, M., Kuusela, S., & Lönnberg, H. (1998). Kinetics and mechanisms for the cleavage and isomerization of the phosphodiester bonds of RNA by bronsted acids and bases. Chemical Reviews, 98 (3), 961-990.
- Pradeepkumar, PI, Höbartner, C., Baum, D., & Silverman, S. (2008). DNA-Catalyzed Formation of Nucleopeptide Linkages. Angewandte Chemie International Edition, 47 (9), 1753–1757.
- Soderberg, T. (2010). Organic Chemistry With a Biological Emphasis Volume II (Vol. II). Minnesota: University of Minnesota Morris Digital Well. Retrieved from www.digitalcommons.morris.umn.edu