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

Chitra Narayanan, Donald Gagné, Kimberly A. Reynolds, Nicolas Doucet

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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.

Original languageEnglish (US)
Article number3207
JournalScientific reports
Issue number1
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Conserved amino acid networks modulate discrete functional properties in an enzyme superfamily'. Together they form a unique fingerprint.

Cite this