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Article Dans Une Revue PLoS ONE Année : 2019

Nucleotide substrate binding characterization in human pancreatic-type ribonucleases.

Résumé

Human genome contains a group of more than a dozen similar genes with diverse biological functions including antiviral, antibacterial and angiogenesis activities. The characterized gene products of this group show significant sequence similarity and a common structural fold associated with binding and cleavage of ribonucleic acid (RNA) substrates. Therefore, these proteins have been categorized as members of human pancreatic-type ribonucleases (hRNases). hRNases differ in cell/tissue localization and display distinct substrate binding preferences and a wide range of ribonucleolytic catalytic efficiencies. Limited information is available about structural and dynamical properties that influence this diversity among these homologous RNases. Here, we use computer simulations to characterize substrate interactions, electrostatics and dynamical properties of hRNases 1-7 associated with binding to two nucleotide substrates (ACAC and AUAU). Results indicate that even with complete conservation of active-site catalytic triad associated with ribonucleolytic activity, these enzymes show significant differences in substrate interactions. Detailed characterization suggests that in addition to binding site electrostatic and van der Waals interactions, dynamics of distal regions may also play a role in binding. Another key insight is that a small difference in temperature of 300 K (used in experimental studies) and 310 K (physiological temperature) shows significant changes in enzyme-substrate interactions.
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Dates et versions

pasteur-02273417 , version 1 (28-08-2019)

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Khushboo Bafna, Chitra Narayanan, S Chakra Chennubhotla, Nicolas Doucet, Pratul Agarwal. Nucleotide substrate binding characterization in human pancreatic-type ribonucleases.. PLoS ONE, 2019, 14 (8), pp.e0220037. ⟨10.1371/journal.pone.0220037⟩. ⟨pasteur-02273417⟩

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