Maintenance of native-like protein dynamics may not be required for engineering functional proteins.

Published

Journal Article

Proteins are dynamic systems, and understanding dynamics is critical for fully understanding protein function. Therefore, the question of whether laboratory engineering has an impact on protein dynamics is of general interest. Here, we demonstrate that two homologous, naturally evolved enzymes with high degrees of structural and functional conservation also exhibit conserved dynamics. Their similar set of slow timescale dynamics is highly restricted, consistent with evolutionary conservation of a functionally important feature. However, we also show that dynamics of a laboratory-engineered chimeric enzyme obtained by recombination of the two homologs exhibits striking difference on the millisecond timescale, despite function and high-resolution crystal structure (1.05 Å) being conserved. The laboratory-engineered chimera is thus functionally tolerant to modified dynamics on the timescale of catalytic turnover. Tolerance to dynamic variation implies that maintenance of native-like protein dynamics may not be required when engineering functional proteins.

Full Text

Duke Authors

Cited Authors

  • Gobeil, SMC; Clouthier, CM; Park, J; Gagné, D; Berghuis, AM; Doucet, N; Pelletier, JN

Published Date

  • October 2014

Published In

Volume / Issue

  • 21 / 10

Start / End Page

  • 1330 - 1340

PubMed ID

  • 25200606

Pubmed Central ID

  • 25200606

Electronic International Standard Serial Number (EISSN)

  • 1879-1301

International Standard Serial Number (ISSN)

  • 1074-5521

Digital Object Identifier (DOI)

  • 10.1016/j.chembiol.2014.07.016

Language

  • eng