Conservation of Dynamics Associated with Biological Function in an Enzyme Superfamily

Chitra Narayanan (1) , David Bernard (1) , Khushboo Bafna (2) , Donald Gagné (1) , Chakra Chennubhotla (3) , Nicolas Doucet (1, 4, 5) , Pratul Agarwal (6, 2)

1 INRS-IAF - Institut Armand Frappier
2 The University of Tennessee [Knoxville]
3 University of Pittsburgh School of Medicine
4 PROTEO, The Quebec Network for Research on Protein Function, Engineering, and Applications
5 McGill University = Université McGill [Montréal, Canada]
6 ORNL - Oak Ridge National Laboratory [Oak Ridge]

Enzyme superfamily members that share common chemical and/or biological functions also share common features. While the role of structure is well characterized, the link between enzyme function and dynamics is not well understood. We present a systematic characterization of intrinsic dynamics of over 20 members of the pancreatic-type RNase superfamily, which share a common structural fold. This study is motivated by the fact that the range of chemical activity as well as molecular motions of RNase homologs spans over 105 folds. Dynamics was characterized using a combination of nuclear magnetic resonance experiments and computer simulations. Phylogenetic clustering led to the grouping of sequences into functionally distinct subfamilies. Detailed characterization of the diverse RNases showed conserved dynamical traits for enzymes within subfamilies. These results suggest that selective pressure for the conservation of dynamical behavior, among other factors, may be linked to the distinct chemical and biological functions in an enzyme superfamily.

Keywords: computer simulations; enzyme catalysis; nuclear magnetic resonance; pancreatic-type ribonucleases; protein dynamics; superfamily

Domains: Life Sciences [q-bio]

Chitra Narayanan, David Bernard, Khushboo Bafna, Donald Gagné, Chakra Chennubhotla, et al.. Conservation of Dynamics Associated with Biological Function in an Enzyme Superfamily. Structure, 2018, 26 (3), pp.426 - 436.e3. ⟨10.1016/j.str.2018.01.015⟩. ⟨pasteur-01856081⟩