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

Lindqvist, Martina; Sandström, Karin; Liepins, Vilnis; Strömberg, Roger; Gräslund, Astrid

doi:10.1017/s1355838201002576

Cited by 9 publications

(7 citation statements)

References 33 publications

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“…Concentrations of Cd 2+ above 1 mM inhibit the ribozyme reaction with a steep concentration dependence (see, e.g., Figures S4 and S5A). The small Cd 2+ stimulation observed for the U258 variant ribozymes is consistent with coordination of a metal ion important for structural stability, as proposed by Lindqvist et al [78]. …”

Section: Resultssupporting

confidence: 86%

Functional Identification of Catalytic Metal Ion Binding Sites within RNA

et al. 2005

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The viability of living systems depends inextricably on enzymes that catalyze phosphoryl transfer reactions. For many enzymes in this class, including several ribozymes, divalent metal ions serve as obligate cofactors. Understanding how metal ions mediate catalysis requires elucidation of metal ion interactions with both the enzyme and the substrate(s). In the Tetrahymena group I intron, previous work using atomic mutagenesis and quantitative analysis of metal ion rescue behavior identified three metal ions (MA, MB, and MC) that make five interactions with the ribozyme substrates in the reaction's transition state. Here, we combine substrate atomic mutagenesis with site-specific phosphorothioate substitutions in the ribozyme backbone to develop a powerful, general strategy for defining the ligands of catalytic metal ions within RNA. In applying this strategy to the Tetrahymena group I intron, we have identified the pro-S P phosphoryl oxygen at nucleotide C262 as a ribozyme ligand for MC. Our findings establish a direct connection between the ribozyme core and the functionally defined model of the chemical transition state, thereby extending the known set of transition-state interactions and providing information critical for the application of the recent group I intron crystallographic structures to the understanding of catalysis.

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Section: Resultssupporting

confidence: 86%

Functional Identification of Catalytic Metal Ion Binding Sites within RNA

et al. 2005

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“…Hydroxide formation within the coordination sphere of Mg 2+ is also believed to reduce the coordination number . Related issues regarding the use of Mn 2+ in rescue experiments have recently been indicated in different contexts. ,,, …”

Section: 45 Water−hydroxide Equilibria and The “Metal-ion Switch Expe...mentioning

confidence: 99%

Alternative Roles for Metal Ions in Enzyme Catalysis and the Implications for Ribozyme Chemistry

2006

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Contents 1. Introduction 97 2. Increased Complexity of Group-Transfer Catalysis by Metalloenzymes 98 3. Metal-Ion Binding Sites in Proteins and Ribozymes 99 3.1. Metal-Ion Binding Sites in Proteins 99 3.2. Metal-Ion Binding Sites in RNA 100 4. Promoting Catalysis with Charge: Electrostatic Effects 101 4.1. Localized Charges Can Modulate the Reactivity of Enzyme Functional Groups 101 4.2. Electrostatic Induction by Divalent Metal Ions 103 4.3. Switching Charge Types in Proteins: Metals for Lysine and Vice Versa 103 4.4. Electrostatic Induction of pK a Shifts in Nucleic Acids: Lessons from Nucleobase Model Systems 104 4.4.1. Modification of Purine Acidity 104 4.4.2. Modification of Pyrimidine Acidity 105 4.4.3. Effects on Backbone Functionalities 105 4.4.4. Additional Reasons for pK a Shifts in Nucleobases 105 4.4.5. Water−Hydroxide Equilibria and the "Metal-Ion Switch Experiment" 105 4.5. Distance Dependence and Additivity of Charge Effects 105 5. Metal-Ion Catalysis through Outer-Sphere Interactions 107 6. Catalysis by Monovalent Metal Ions 108 7. Reduced Solvent Polarity Promotes Reactivity 110 8. Conclusions 110 9. Acknowledgments 111 10. References 111

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“…The structure and function of DNA and RNA strongly depend on their interactions with divalent cations. − These cations are found to interact with different sites at the surface of nucleic acids: phosphate oxygens, sugar oxygens and nucleotides. Besides the fact that the presence of magnesium ions in solution leads to a decrease in the persistence length of DNA and increases the melting temperature of DNA double-helices, , magnesium is also involved in the site-specific hydrolysis of the polyester bond of DNA, both enzymatically − and in protein-free systems, , and in RNA. , It has also been reported that divalent metal cations stimulate the formation of DNA and RNA triple helices , and stabilize other noncanonical structures such as quadruple helices …”

Section: Introductionmentioning

confidence: 99%

“…Besides the fact that the presence of magnesium ions in solution leads to a decrease in the persistence length of DNA 5 and increases the melting temperature of DNA double-helices, 6,7 magnesium is also involved in the site-specific hydrolysis of the polyester bond of DNA, both enzymatically [8][9][10] and in protein-free systems, 11,12 and in RNA. 13,14 It has also been reported that divalent metal cations stimulate the formation of DNA and RNA triple helices 15,16 and stabilize other noncanonical structures such as quadruple helices. 17 To understand the nature of the interaction between nucleic acids and metal cations, a number of computational investigations have recently been made.…”

Section: Introductionmentioning

confidence: 99%

Water-Mediated Magnesium-Guanine Interactions

2002

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Divalent cations, particularly magnesium, play an important role in the stabilization of nucleic acids and in their biochemistry. Of special interest is the strong affinity of a hydrated magnesium ion for guanine. To investigate the nature of this interaction, we calculated the interaction energy (IE) for eight optimized complexes in which tetra-, penta-, and hexahydrated magnesium ions were initially placed in the plane of guanine near the O6 and N7 binding sites. Results at the RHF/6-311G**//RHF/6-311++G** level indicate that the guaninetetrahydrated magnesium ion complex has the highest value of the IE. However, the formation of the tetrahydrated magnesium ion from a hexahydrated ion decreases the energy of this complex and, overall, the hexahydrated ion is considered to be more stable. We also investigated the binding site of a hexahydrated magnesium ion located in a high-resolution crystal structure of the dodecamer [d(CGCGAATTCGCG)] 2 . Complexes of the hexahydrated magnesium ion with the individual and combined G2 and G22 bases extracted from the crystal structure were also considered and Natural Energy Decomposition Analysis used to partition the IEs. The results show that water-mediated charge transfer from guanine to magnesium plays an important role in the stabilization of these guanine-water-magnesium complexes and occurs by a cooperative mechanism.

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

Cited by 9 publications

References 33 publications

Functional Identification of Catalytic Metal Ion Binding Sites within RNA

Functional Identification of Catalytic Metal Ion Binding Sites within RNA

Alternative Roles for Metal Ions in Enzyme Catalysis and the Implications for Ribozyme Chemistry

Water-Mediated Magnesium-Guanine Interactions

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