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545945 occurrences (No.21 in the rank) during 5 years in the PubMed. [cache]
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545945 occurrences (No.21 in the rank) during 5 years in the PubMed. [cache]
| 254) Therefore, the new approach is able to illustrate the diversity of the underlying mechanisms when the strength of feedback inhibition by the effector(s) is modulated, providing useful information that has potential applications in engineering heteromultimeric allosteric regulation. |
| PMID:24279729 DOI:10.1080/07391102.2013.855145 |
| 2015 Journal of biomolecular structure & dynamics |
| * Exploring signal transduction in heteromultimeric protein based on energy dissipation model. |
| - Dynamic intersubunit interactions are key elements in the regulation of many biological systems. A better understanding of how subunits interact with each other and how their interactions are related to dynamic protein structure is a fundamental task in biology. In this paper, a heteromultimeric allosteric protein, Corynebacterium glutamicum aspartokinase, is used as a model system to explore the signal transduction involved in intersubunit interactions and allosteric communication with an emphasis on the intersubunit signaling process. For this purpose, energy dissipation simulation and network construction are conducted for each subunit and the whole protein. Comparison with experimental results shows that the new approach is able to predict all the mutation sites that have been experimentally proved to desensitize allosteric regulation of the enzyme. Additionally, analysis revealed that the function of the effector threonine is to facilitate the binding of the two subunits without contributing to the allosteric communication. During the allosteric regulation upon the binding of the effector lysine, signals can be transferred from the β-subunit to the catalytic site of the α-subunit through both a direct way of intersubunit signal transduction, and an indirect way: first, to the regulatory region of the α-subunit by intersubunit signal transduction and then to the catalytic region by intramolecular signal transduction. Therefore, the new approach is able to illustrate the diversity of the underlying mechanisms when the strength of feedback inhibition by the effector(s) is modulated, providing useful information that has potential applications in engineering heteromultimeric allosteric regulation. |
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