Physicochemical Properties of Ion Pairs of  Biological Macromolecules

Iwahara, Junji; Esadze, Alexandre; Zandarashvili, Levani

doi:10.3390/biom5042435

Cited by 35 publications

(33 citation statements)

References 172 publications

(268 reference statements)

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“…Interactions with the DNA backbones and the DNA bases, involving salt bridges or hydrogen bonds, have lifetimes that are typically of the order of tens to hundreds of picoseconds. This is in line with recent NMR and simulations studies of the dynamics of lysine salt bridges in protein/DNA complexes (5,41,42). A very recent extension of this work shows that, in contrast, arginines bound to guanine in a bidentate manner within a Zn-finger complex are much less dynamic (43).…”

Section: Discussionsupporting

confidence: 90%

Protein–DNA interfaces: a molecular dynamics analysis of time-dependent recognition processes for three transcription factors

Éthève¹,

Martin²,

Lavery³

2016

Nucleic Acids Res

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We have studied the dynamics of three transcription factor–DNA complexes using all-atom, microsecond-scale MD simulations. In each case, the salt bridges and hydrogen bond interactions formed at the protein–DNA interface are found to be dynamic, with lifetimes typically in the range of tens to hundreds of picoseconds, although some interactions, notably those involving specific binding to DNA bases, can be a hundred times longer lived. Depending on the complex studied, this dynamics may or may not lead to the existence of distinct conformational substates. Using a sequence threading technique, it has been possible to determine whether DNA sequence recognition is sensitive or not to such conformational changes, and, in one case, to show that recognition appears to be locally dependent on protein-mediated cation distributions.

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Section: Discussionsupporting

confidence: 90%

Protein–DNA interfaces: a molecular dynamics analysis of time-dependent recognition processes for three transcription factors

Éthève¹,

Martin²,

Lavery³

2016

Nucleic Acids Res

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“…Oxygen-to-sulfur substitutions might also perturb the dynamic equilibrium of the contact ion-pair (CIP) and solvent-separated ion-pair (SIP) states. [21] As we recently demonstrated, the intermolecular ion pairs of Lys side-chain and DNA phosphate groups undergoes dynamic transitions between the CIP and SIP states on a sub-nanosecond timescale. [12] Oxygen-to-sulfur substitution in DNA phosphate might shift the CIP-SIP equilibrium of the intermolecular ion pair toward the SIP state, mobilizing the Lys NH 3 + group.…”

Section: Discussionmentioning

confidence: 99%

Stereospecific Effects of Oxygen‐to‐Sulfur Substitution in DNA Phosphate on Ion Pair Dynamics and Protein–DNA Affinity

et al. 2016

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Oxygen-to-sulfur substitutions in DNA phosphate often enhance affinity for DNA-binding proteins. Our previous studies have suggested that this effect of sulfur substitution of both OP1 and OP2 atoms is due to an entropic gain associated with enhanced ion-pair dynamics. In this work, we studied stereospecific effects of single sulfur substitution of either the OP1 or OP2 atom in DNA phosphate at the Lys57 interaction site of the Antennapedia homeodomain-DNA complex. By crystallography, we obtained the structural information on the RP and SP diastereomers of the phosphoromonothioate and their interaction with Lys57. By fluorescence-based assays, we found significant affinity enhancement upon sulfur substitution of the OP2 atom. By NMR spectroscopy, we found significant mobilization of the Lys57 side-chain NH3+ group upon sulfur substitution of the OP2 atom. These data provide further mechanistic insight into the affinity enhancement by oxygen-to-sulfur substitution in DNA phosphate.

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“…In fact, our previous NMR and molecular dynamics studies showed that the Lys 15 NH 3 + groups that exhibit sizable h3 J NP coupling with the DNA 31 P nuclei undergo dynamic transitions on a sub-nanosecond timescale between the contact ion-pair and solvent-separated ion-pair states. 7,9,31 …”

mentioning

confidence: 99%

Residence Times of Molecular Complexes in Solution from NMR Data of Intermolecular Hydrogen-Bond Scalar Coupling

Zandarashvili

Esadze

Kemme

et al. 2016

J. Phys. Chem. Lett.

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The residence times of molecular complexes in solution are important for understanding biomolecular functions and drug actions. Here we show that NMR data of intermolecular hydrogen-bond scalar couplings can yield information on the residence times of molecular complexes in solution. The molecular exchange of binding partners via the breakage and reformation of a complex causes self-decoupling of intermolecular hydrogen-bond scalar couplings, and this self-decoupling effect depends on the residence time of the complex. For protein–DNA complexes, we investigated the salt-concentration dependence of intermolecular hydrogen-bond scalar couplings between the protein side-chain 15N and DNA phosphate 31P nuclei, from which the residence times were analyzed. The results were consistent with those obtained by 15Nz-exchange spectroscopy. This self-decoupling-based kinetic analysis is unique in that it does not require any different signatures for the states involved in the exchange, whereas such conditions are crucial for kinetic analyses by typical NMR and other methods.

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Physicochemical Properties of Ion Pairs of Biological Macromolecules

Cited by 35 publications

References 172 publications

Protein–DNA interfaces: a molecular dynamics analysis of time-dependent recognition processes for three transcription factors

Protein–DNA interfaces: a molecular dynamics analysis of time-dependent recognition processes for three transcription factors

Stereospecific Effects of Oxygen‐to‐Sulfur Substitution in DNA Phosphate on Ion Pair Dynamics and Protein–DNA Affinity

Residence Times of Molecular Complexes in Solution from NMR Data of Intermolecular Hydrogen-Bond Scalar Coupling

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