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Uncovering similar conformational exchange residue clusters in eosinophil-like ribonucleases

Bernard, David N.; Gagné, Donald; Doucet, Nicolas . Uncovering similar conformational exchange residue clusters in eosinophil-like ribonucleases In: 2nd Protein Engineering Canada Conference (PEC), Juin 2016, Ottawa.

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Résumé

Enzymes are increasingly being used in pharmaceutical and indus trial environments, particularly as greener and more efficient alternatives to chemical catalyst s. However, engineering new enzyme reactions is an arduous and inefficient process, mainly because the predictable outcome of protein engineering on 3D structure, function and dynamics r emains elusive. Recent experimental evidence suggests that conformational exchange may be involved in promoting catalysis in many enzyme system s, but the mechanisms underlying this atomic flexibility remain unclear. It is still unknown whether sequence and/or structure are evolutionarily conserved to promote flexibility events linked to biological function among protein homologs. Understanding phenomena underlying protein dynamics is thus an important step in facilitating protein engineering. In order to tackle these interrogations, we have u sed NMR to characterize the millisecond timescale conformational exchange in various member s of the ribonuclease A superfamily. While these enzymes d isplay very similar structure , their evolutionary distance and diversified biological activities complicate flexibility-functi on analyses. To solve this issue, we have investigated mammalian homologs of human ribonuclease 3 (Eosino phil Cationic Protein, ECP), comparing the human enzyme with its close ECP homologs from Pon go pygmaeus and Macaca fascicularis. Our findings show that conformational exchange in the monkey enzymes strongly resembles that of their human counterpart, providing insights i nto the effects of sequence and phylogenetic diversity on protein dynamics. Further experiments are required to determine the exact biological roles of these enzymes and their dependence on atomic flexibility.

Type de document: Document issu d'une conférence ou d'un atelier
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 25 juin 2018 13:55
Dernière modification: 25 juin 2018 13:55
URI: http://espace.inrs.ca/id/eprint/5783

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