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Evolutionarily Related Dihydrofolate Reductases Perform Coequal Functions Yet Show Divergence in Their Trajectories

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Abstract

The enzyme dihydrofolate reductase (DHFR) catalyzes NADPH dependent reduction of dihydrofolate to tetrahydrofolate. It plays a crucial role in the DNA synthesis. The investigation of evolution of DHFR generates immense curiosity. It aids in predicting how the enzyme has adapted to the surroundings of various cell types. In spite of great similarity in the structure of E. coli DHFR and human DHFR, their primary sequences are divergent to a great extent, which is evident in variations in the kinetics mechanism of their catalysis. In presence of physiological levels of ligands, they possess distinct kinetics and different rate limiting steps. We have reviewed the process of their unfolding and refolding, their behaviour in denaturing conditions and in presence of various chaperones. Although there is structural similarity between these two homologous enzymes yet they have established distinct mechanisms to accomplish the coequal functions.

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Acknowledgements

The authors acknowledge the financial assistance provided by Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India.

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Authors and Affiliations

  1. Molecular Biophysics Lab, Amity Institute of Biotechnology, Amity University, Sector 125, Noida, Uttar Pradesh, 201313, India

    Naira Rashid & Pratima Chaudhuri (Chattopadhyay)

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  1. Naira Rashid
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  2. Pratima Chaudhuri (Chattopadhyay)
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Correspondence to Pratima Chaudhuri (Chattopadhyay).

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Rashid, N., Chaudhuri (Chattopadhyay), P. Evolutionarily Related Dihydrofolate Reductases Perform Coequal Functions Yet Show Divergence in Their Trajectories. Protein J 37, 301–310 (2018). https://doi.org/10.1007/s10930-018-9784-8

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