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    Item type:Publication, Access status: without files ,
    Analysis of co-evolved interaction network of E.coli aspartokinase III and regulation of allosteric progress using energy transduction
    (2022-02-01)
    Wang, Shi-Zhen
    ;
    Ma, Cheng-Wei
    ;
    Zeng, An-Ping
    Understanding co-evolved interaction network involved in allosteric regulation of kinase is of fundamental interest. Here, with aspartokinase III (AKIII) from E. coli as a model system the rearrangement of side-chain interactions upon inhibitor binding are identified by comparing amino acid interaction networks for both the R- and T-states of AKIII. Steered molecular dynamics simulation is then applied to study the dynamic conformational change and the energy transduction process, which is followed by identification of co-evolved interaction network involved in the allosteric regulation. To verify the co-evolved allo-network, mutations of AKIII are examined and modulation of the allosteric regulation is demonstrated by site-directed mutagenesis of the key residues. As illustrated, this study proposes a strategy to identify the co-evolved interaction network that drives the allosteric process. The key feature of the strategy is that key residues involved in the energy transfer pathway can be quickly determined by co-evolutionary analysis of the interfacial interactions of motifs.
    Publicationtype: Journal Article
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    Item type:Publication, Access status: with files ,
    Dynamic energy correlation analysis of E. coli aspartokinase III and alteration of allosteric regulation by manipulating energy transduction pathways
    (Wiley-Blackwell, 2021-03-02)
    Wang, Shizhen
    ;
    Ma, Cheng-Wei
    ;
    Zeng, An-Ping
    Conformational change associated with allosteric regulation in a protein is ultimately driven by energy transformation. However, little is known about the latter process. In this work, we combined steered molecular dynamics simulations and sequence conservation analysis to investigate the conformational changes and energy transformation in the allosteric enzyme aspartokinase III (AK III) from Escherichia coli. Correlation analysis of energy change at residue level indicated significant transformation between electrostatic energy and dihedral angle energy during the allosteric regulation. Key amino acid residues located in the corresponding energy transduction pathways were identified by dynamic energy correlation analysis. To verify their functions, residues with a high energy correlation in the pathways were altered and their effects on allosteric regulation of AKIII were determined. This study sheds new insights into energy transformation during allosteric regulation of AK III and proposes a strategy to identify key residues that are involved in intramolecular energy transduction and thus in driving the allosteric process.
    Publicationtype: Journal Article
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