Zwei Metallionen behindern sich kaum bei der Koordination an ein Purin

Knobloch, Bernd; Sigel, Roland K. O.; Lippert, Bernhard; Sigel, Helmut

doi:10.1002/ange.200453987

Cited by 5 publications

(2 citation statements)

References 32 publications

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“…For cases in which two or more neighboring phosphate groups bind to Mg 2 + ions, these then tend to cluster close together, as observed in the loop E motif, [14] the active site of group I introns, [73] as well as at a single nucleobase. [76] The findings presented here are in good agreement with all of these observations, and furthermore, they assign the first quantitative evaluation to these phenomena.…”

Section: Discussionsupporting

confidence: 90%

Acid–Base and Metal‐Ion Binding Properties of the RNA Dinucleotide Uridylyl‐(5′→3′)‐[5′]uridylate (pUpU³⁻)

Knobloch

Suliga

Okruszek

et al. 2005

Chemistry A European J

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It is well known that Mg2+ and other divalent metal ions bind to the phosphate groups of nucleic acids. Subtle differences in the coordination properties of these metal ions to RNA, especially to ribozymes, determine whether they either promote or inhibit catalytic activity. The ability of metal ions to coordinate simultaneously with two neighboring phosphate groups is important for ribozyme structure and activity. However, such an interaction has not yet been quantified. Here, we have performed potentiometric pH titrations to determine the acidity constants of the protonated dinucleotide H2(pUpU)-, as well as the binding properties of pUpU3- towards Mg2+, Mn2+, Cd2+, Zn2+, and Pb2+. Whereas Mg2+, Mn2+, and Cd2+ only bind to the more basic 5'-terminal phosphate group, Pb2+, and to a certain extent also Zn2+, show a remarkably enhanced stability of the [M(pUpU)]- complex. This can be attributed to the formation of a macrochelate by bridging the two phosphate groups within this dinucleotide by these metal ions. Such a macrochelate is also possible in an oligonucleotide, because the basic structural units are the same, despite the difference in charge. The formation degrees of the macrochelated species of [Zn(pUpU)]- and [Pb(pUpU)]- amount to around 25 and 90 %, respectively. These findings are important in the context of ribozyme and DNAzyme catalysis, and explain, for example, why the leadzyme could be selected in the first place, and why this artificial ribozyme is inhibited by other divalent metal ions, such as Mg2+.

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Section: Discussionsupporting

confidence: 90%

Acid–Base and Metal‐Ion Binding Properties of the RNA Dinucleotide Uridylyl‐(5′→3′)‐[5′]uridylate (pUpU³⁻)

Knobloch

Suliga

Okruszek

et al. 2005

Chemistry A European J

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“…Given that average values have been used and (in part) differently charged complexes are compared, agreement of these two approaches is reasonable. Comparison of the acidifying influence of Pt II entities at N7 of 9-ethylguanine on the proton at N1 (DpK a = 1.40 AE 0.06 [36] ) further supports the notion proposed by Sigel that the acidifying effects of metal ions at N1 or N7 of purines are "reciprocal". [32] Regarding the possible relevance of a N1-metalated rare guanine tautomer in a putative base-pairing step that involves the protonated N7 position of guanine, the relative low pK a of this proton (4-5) would seem to make such a scenario unlikely in water at physiological pH.…”

Section: Crystal Structure Analysis Of {Trans-supporting

confidence: 78%

Pt^II Coordination to N1 of 9‐Methylguanine: Why it Facilitates Binding of Additional Metal Ions to the Purine Ring

Müller¹,

Shen²,

Miguel³

et al. 2011

Chemistry A European J

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The preparation and X-ray crystal structure analysis of {trans-[Pt(MeNH(2))(2)(9-MeG-N1)(2)]}⋅{3 K(2)[Pt(CN)(4)]}⋅6 H(2)O (3 a) (with 9-MeG being the anion of 9-methylguanine, 9-MeGH) are reported. The title compound was obtained by treating [Pt(dien)(9-MeGH-N7)](2+) (1; dien=diethylenetriamine) with trans-[Pt(MeNH(2))(2)(H(2)O)(2)](2+) at pH 9.6, 60 °C, and subsequent removal of the [(dien)Pt(II)] entities by treatment with an excess amount of KCN, which converts the latter to [Pt(CN)(4)](2-). Cocrystallization of K(2)[Pt(CN)(4)] with trans-[Pt(MeNH(2))(2)(9-MeG-N1)(2)] is a consequence of the increase in basicity of the guanine ligand following its deprotonation and Pt coordination at N1. This increase in basicity is reflected in the pK(a) values of trans-[Pt(MeNH(2))(2)(9-MeGH-N1)(2)](2+) (4.4±0.1 and 3.3±0.4). The crystal structure of 3 a reveals rare (N7,O6 chelate) and unconventional (N2,C2,N3) binding patterns of K(+) to the guaninato ligands. DFT calculations confirm that K(+) binding to the sugar edge of guanine for a N1-platinated guanine anion is a realistic option, thus ruling against a simple packing effect in the solid-state structure of 3 a. The linkage isomer of 3 a, trans-[Pt(MeNH(2))(2)(9-MeG-N7)(2)] (6 a) has likewise been isolated, and its acid-base properties determined. Compound 6 a is more basic than 3 a by more than 4 log units. Binding of metal entities to the N7 positions of 9-MeG in 3 a has been studied in detail for [(NH(3))(3)Pt(II)], trans-[(NH(3))(2)Pt(II)], and [(en)Pd(II)] (en=ethylenediamine) by using (1)H NMR spectroscopy. Without exception, binding of the second metal takes place at N7, but formation of a molecular guanine square with trans-[(Me(2)NH(2))Pt(II)] cross-linking N1 positions and trans-[(NH(3))(2)Pt(II)] cross-linking N7 positions could not be confirmed unambiguously, despite the fact that calculations are fully consistent with its existence.

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Solution Structure of Domain 6 from a Self‐Splicing Group II Intron Ribozyme: A Mg²⁺ Binding Site is Located Close to the Stacked Branch Adenosine

et al. 2007

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Group II intron self-splicing is essential for correct expression of organellar genes in plants, fungi, and yeast, as well as of bacterial genes. Self-excision of these autocatalytic introns from the primary RNA transcript is achieved in a two-step mechanism apparently analogous to the one of the eukaryotic spliceosome. The 2'-OH of a conserved adenosine (the branch point) located within domain 6 (D6) acts as the nucleophile in the first step of splicing. Despite the biological importance of group II introns, little is known about their structural organization and usage of metal ions in catalysis. Here we report the first solution structure of a catalytically active D6 construct encompassing the branch point and the neighboring helical regions from the mitochondrial yeast intron ai5 . The branch adenosine is the single unpaired nucleotide, and, in contrast to the spliceosomal branch site, resides within the helix being partially stacked between the two flanking GU wobble pairs. We identified a novel prominent Mg2+ binding site in the major groove of the branch site. Importantly, Mg2+ addition does not impair stacking of the branch-adenosine, but in contrast rather strengthens the interaction with the flanking uridines, as shown by NMR-and fluorescence studies. This means, that domain 6 presents the branch adenosine in a stacked fashion to the core of group II introns upon folding to the active conformation.

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Zwei Metallionen behindern sich kaum bei der Koordination an ein Purin

Cited by 5 publications

References 32 publications

Acid–Base and Metal‐Ion Binding Properties of the RNA Dinucleotide Uridylyl‐(5′→3′)‐[5′]uridylate (pUpU³⁻)

Acid–Base and Metal‐Ion Binding Properties of the RNA Dinucleotide Uridylyl‐(5′→3′)‐[5′]uridylate (pUpU³⁻)

Pt^II Coordination to N1 of 9‐Methylguanine: Why it Facilitates Binding of Additional Metal Ions to the Purine Ring

Solution Structure of Domain 6 from a Self‐Splicing Group II Intron Ribozyme: A Mg²⁺ Binding Site is Located Close to the Stacked Branch Adenosine

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Zwei Metallionen behindern sich kaum bei der Koordination an ein Purin

Cited by 5 publications

References 32 publications

Acid–Base and Metal‐Ion Binding Properties of the RNA Dinucleotide Uridylyl‐(5′→3′)‐[5′]uridylate (pUpU3−)

Acid–Base and Metal‐Ion Binding Properties of the RNA Dinucleotide Uridylyl‐(5′→3′)‐[5′]uridylate (pUpU3−)

PtII Coordination to N1 of 9‐Methylguanine: Why it Facilitates Binding of Additional Metal Ions to the Purine Ring

Solution Structure of Domain 6 from a Self‐Splicing Group II Intron Ribozyme: A Mg2+ Binding Site is Located Close to the Stacked Branch Adenosine

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Acid–Base and Metal‐Ion Binding Properties of the RNA Dinucleotide Uridylyl‐(5′→3′)‐[5′]uridylate (pUpU³⁻)

Acid–Base and Metal‐Ion Binding Properties of the RNA Dinucleotide Uridylyl‐(5′→3′)‐[5′]uridylate (pUpU³⁻)

Pt^II Coordination to N1 of 9‐Methylguanine: Why it Facilitates Binding of Additional Metal Ions to the Purine Ring

Solution Structure of Domain 6 from a Self‐Splicing Group II Intron Ribozyme: A Mg²⁺ Binding Site is Located Close to the Stacked Branch Adenosine