Deciphering the structural basis of the broad substrate specificity of myo-inositol monophosphatase (IMP) from Cicer arietinum
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Title |
Deciphering the structural basis of the broad substrate specificity of myo-inositol monophosphatase (IMP) from Cicer arietinum
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Creator |
Yadav, Prakarsh K.
Salvi, Prafull Kamble, Nitin Uttam Petla, Bhanu Prakash Majee, Manoj Saxena, Saurabh C. |
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Subject |
Myo-inositol monophosphatase
Broad substrate catalysis Structural analysis Molecular simulation Molecular docking |
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Description |
Accepted date: 11 November 2019
Myo-inositol monophosphatase (IMP) is a crucial enzyme in the inositol biosynthetic pathway that dephosphorylates myo-inositol 1-phosphate and other inositol phosphate derivative compounds to maintain the homeostasis of cellular inositol pool. In our previous research, we have biochemically and functionally characterized IMP enzyme from chickpea (CaIMP), which was able to catalyze diverse substrates. We cloned, overexpressed recombinant CaIMP protein and purified it and further characterized the CaIMP with its three main substrates viz. galactose 1-P, inositol 6-P and fructose 1,6-bisP. Homology model of CaIMP was generated to elucidate the factors contributing to the broad substrate specificity of the protein. The active site of the CaIMP protein was analysed with respect to its interactions with the proposed substrates. Structural features such as, high B-factor and flexible loop regions in the active site, inspired further investigation into the static and dynamic behaviour of the active site of CaIMP protein. The electrostatic biding of each of the key substrates was assessed through molecular docking. Furthermore, molecular dynamics simulations showed that these interactions indeed were stable for extended periods of time under physiological conditions. These experiments conclusively allowed us to establish the primary factors contributing to the promiscuity in substrate binding by CaIMP protein. This work was supported by the Science and Engineering Research Board (SERB), Government of India under the scheme of “Start Up Research Grant (Young Scientist) - Elucidating the Functional and Regulatory Aspects of inositol Monophosphatase like Proteins (IMPL1 and IMPL2) from drought tolerant legume Chickpea (Cicer arietinum)” (Grant no: YSS/2014/001012/LS). |
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Date |
2019-11-27T06:28:27Z
2019-11-27T06:28:27Z 2020 |
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Type |
Article
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Identifier |
International Journal Biological Macromolecules, 151: 967-975
0141-8130 http://223.31.159.10:8080/jspui/handle/123456789/1015 https://www.sciencedirect.com/science/article/pii/S0141813019363809?via%3Dihub https://doi.org/10.1016/j.ijbiomac.2019.11.098 |
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Language |
en_US
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Format |
application/pdf
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Publisher |
Elsevier B.V.
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