Metal Activation of Enzymes in Nucleic Acid Biochemistry

Increasing Growth Yield and Decreasing Acetylation in Escherichia coli by Optimizing the Carbon-to-Magnesium Ratio in Peptide-Based Media

“…Magnesium is also required to make ATP biologically active and participates in catalysis of certain enzymatic reactions through either direct or indirect mechanisms (14,15). Almost half of total magnesium is found associated with nucleoside triphosphates (NTPs) (primarily ATP) (11), approximately one-third is associated with the cell wall (13), and the remaining is bound to various molecules or free in the cytoplasm.…”

Bis[2,6-bis(1-methyl-1H-benzimidazol-2-yl-κN3)pyridine-κN]zinc dipicrate methanol disolvate

“…For the applications of benzimidazole derivatives, see : Horton et al (2003); Wang et al (1994); Cowan (1998); Liu et al (2004Liu et al ( , 2011Wright (1951). For a related crystal structure, see: Huang et al (2010).…”

Specific metal-ion binding sites in a model of the P4-P6 triple-helical domain of a group I intron

“…Large ribozymes require divalent metal ions for tertiary folding and structure+ Positively charged ions screen the negative charge of the RNA backbone and reduce repulsions between electronegative groups within the RNA structure+ Most of the divalent metal ions bind the RNA in a nonspecific manner+ However, a subset interacts with functionally important metal binding sites, where the metal ion can play a structural and/or catalytical role, interacting with electron pair donors of the bases and sugar-phosphate backbone (Feig & Uhlenbeck, 1999)+ The metal ion may bind to pockets already existing in the secondary structure, or to sites that appear during tertiary folding (Tinoco & Bustamante, 1999)+ Specific interactions between magnesium and nonbridging phosphate oxygens can be revealed by phosphorothioate interference experiments+ In these, one utilizes the fact that a hard Lewis acid (magnesium) shows a much stronger affinity for a hard Lewis base (oxygen) as compared to a soft Lewis base (sulfur)+ If a phosphate oxygen is part of a specific metal binding site, where a magnesium ion crucial for ribozyme structure and/or catalysis is situated, a sulfur substitution at that position results in a reduced or abolished activity of the ribozyme+ Manganese, being a less hard Lewis acid than magnesium, has a greater propensity to interact with sulfur and can thereby often replace magnesium and restore activity+ This kind of manganese rescue implies that the site of interest is a specific magnesium-binding site of importance for ribozyme structure and/or activity+ Generally, the exchange of ligand atom (oxygen r sulfur) and metal-ion identity (magnesium r manganese) of a phosphorothioate interference experiment does not have any major influence on the original structure of the RNA molecule (Feig & Uhlenbeck, 1999;Feig, 2000;Maderia et al+, 2000b)+ However, recent studies have in some cases described substantial effects on RNA structure as a consequence of phosphorothioate substitutions (Horton et al+, 2000;Maderia et al+, 2000a;Smith & Nikonowicz, 2000)+ The effects seem to be localized to regions of irregular secondary structure, where a phosphorothioate substitution might modify the local structure considerably, thus changing the availability of functional groups+ Other studies have shown that a metal-ion switch can lead to RNA-metalion interactions not present in the original structure (Basu & Strobel, 1999;Shan & Herschlag, 2000), this due to the different tendencies of the metal ions in binding various ligands (Cowan, 1998;Bock et al+, 1999)+ The potential structural disruption and/or alternate RNAmetal-ion interactions must be taken into account when interpreting results obtained from phosphorothioate interference experiments+…”