Heterogeneity in winged helix‐turn‐helix and substrate DNA interactions: Insights from theory and experiments

Boral, Aparna; Mitra, Devrani

doi:10.1002/jcb.30369

Cited by 2 publications

(1 citation statement)

References 90 publications

(231 reference statements)

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“…Incidentally, 80% of the identified residues in both the polypeptide chains of the NolR dimer are located either at the recognition helix or the wing region (Figure S2(b)). Interestingly, our recent findings [40] reveal that 92% of the NolR residues - which exhibit the maximum change in eigenvector centrality - are concentrated in the recognition helix and the wing region. Perhaps this is worth mentioning that the eigenvector centrality measure of protein residue information is effective in identifying key amino acid residues involved in the allosteric signaling process [41].…”

Section: Resultsmentioning

confidence: 99%

Anab initioinformation-theoretic approach to proteins and protein-ligand interactions

Nath,

Grewal,

Mitra

et al. 2024

Preprint

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Differing conformational structure of a protein, associated with two distinct signaling states or between ligand-free and ligand-bound states, leads to differing inter-residue interactions and, consequently different biological function. We propose a fresh first-principles information-theoretic approach for studying such proteins and their interactions. Ade novomeasure called protein residue information (PRI), which incorporates details of interactions between all pairs of atoms within and across all residues of the protein, is introduced herein. We formulate a method to calculate the intra-state and inter-state entropy of every residue, needed to determine PRI across any two states of a protein. The intra-state entropy can be determined for every state of a protein possessing one or more states. The inter-state entropy can be calculated pairwise for proteins possessing more than one state. Well-known visualization software allow the computation of conformational change of a particular residue across two different states of a protein. Our formulation takes into account the conformational change of any residue with respect to itself as well as with every other residue. Analyses of twenty eight distinct pairs of proteins from ten distinct classes shows that PRI identifies residues displaying conformational changes bearing influence with respect to itself and all other residues. The identified residues exhibit influential roles in diverse performative features of proteins like stability, allostery, signaling, etc. PRI successfully recovers known experimental results from literature and predicts important roles for hitherto unstudied residues.

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Section: Resultsmentioning

confidence: 99%

Anab initioinformation-theoretic approach to proteins and protein-ligand interactions

Nath,

Grewal,

Mitra

et al. 2024

Preprint

Self Cite

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Substrate DNA Promoting Binding of Mycobacterium tuberculosis MtrA by Facilitating Dimerization and Interpretation of Affinity by Minor Groove Width

Memon,

Fu,

Fan

et al. 2023

Microorganisms

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In order to deepen the understanding of the role and regulation mechanisms of prokaryotic global transcription regulators in complex processes, including virulence, the associations between the affinity and binding sequences of Mycobacterium tuberculosis MtrA have been explored extensively. Analysis of MtrA 294 diversified 26 bp binding sequences revealed that the sequence similarity of fragments was not simply associated with affinity. The unique variation patterns of GC content and periodical and sequential fluctuation of affinity contribution curves were observed along the sequence in this study. Furthermore, docking analysis demonstrated that the structure of the dimer MtrA-DNA (high affinity) was generally consistent with other OmpR family members, while Arg 219 and Gly 220 of the wing domain interacted with the minor groove. The results of the binding box replacement experiment proved that box 2 was essential for binding, which implied the differential roles of the two boxes in the binding process. Furthermore, the results of the substitution of the nucleotide at the 20th and/or 21st positions indicated that the affinity was negatively associated with the value of minor groove width precisely at the 21st position. The dimerization of the unphosphorylated MtrA facilitated by a low-affinity DNA fragment was observed for the first time. However, the proportion of the dimer was associated with the affinity of substrate DNA, which further suggested that the affinity was actually one characteristic of the stability of dimers. Based on the finding of 17 inter-molecule hydrogen bonds identified in the interface of the MtrA dimer, including 8 symmetric complementary ones in the conserved α4-β5-α5 face, we propose that hydrogen bonds should be considered just as important as salt bridges and the hydrophobic patch in the dimerization. Our comprehensive study on a large number of binding fragments with quantitative affinity values provided new insight into the molecular mechanism of dimerization, binding specificity and affinity determination of MtrA and clues for solving the puzzle of how global transcription factors regulate a large quantity of target genes.

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Heterogeneity in winged helix‐turn‐helix and substrate DNA interactions: Insights from theory and experiments

Cited by 2 publications

References 90 publications

Anab initioinformation-theoretic approach to proteins and protein-ligand interactions

Anab initioinformation-theoretic approach to proteins and protein-ligand interactions

Substrate DNA Promoting Binding of Mycobacterium tuberculosis MtrA by Facilitating Dimerization and Interpretation of Affinity by Minor Groove Width

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