Conserved amino acid networks modulate discrete functional properties in an enzyme superfamily.

Chitra Narayanan (1) , Donald Gagné (2, 1) , Kimberly A Reynolds (3) , Nicolas Doucet (4, 1, 5)

1 INRS-IAF - Institut Armand Frappier
2 CUNY - City University of New York [New York]
3 University of Texas Southwestern Medical Center [Dallas]
4 PROTEO, The Quebec Network for Research on Protein Function, Engineering, and Applications
5 GRASP - The Groupe de Recherche Axé sur la Structure des Protéines

In this work, we applied the sequence-based statistical coupling analysis approach to characterize conserved amino acid networks important for biochemical function in the pancreatic-type ribonuclease (ptRNase) superfamily. This superfamily-wide analysis indicates a decomposition of the RNase tertiary structure into spatially distributed yet physically connected networks of co-evolving amino acids, termed sectors. Comparison of this statistics-based description with new NMR experiments data shows that discrete amino acid networks, termed sectors, control the tuning of distinct functional properties in different enzyme homologs. Further, experimental characterization of evolutionarily distant sequences reveals that sequence variation at sector positions can distinguish homologs with a conserved dynamic pattern and optimal catalytic activity from those with altered dynamics and diminished catalytic activities. Taken together, these results provide important insights into the mechanistic design of the ptRNase superfamily, and presents a structural basis for evolutionary tuning of function in functionally diverse enzyme homologs.

Domaines: Sciences du Vivant [q-bio]

Chitra Narayanan, Donald Gagné, Kimberly A Reynolds, Nicolas Doucet. Conserved amino acid networks modulate discrete functional properties in an enzyme superfamily.. Scientific Reports, 2017, 7 (1), pp.3207. ⟨10.1038/s41598-017-03298-4⟩. ⟨pasteur-01574606⟩