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Title: Comparing residue clusters from thermophilic and mesophilic enzymes reveals adaptive mechanisms

Understanding how proteins adapt to function at high temperatures is important for deciphering the energetics that dictate protein stability and folding. While multiple principles important for thermostability have been identified, we lack a unified understanding of how internal protein structural and chemical environment determine qualitative or quantitative impact of evolutionary mutations. In this work we compare equivalent clusters of spatially neighboring residues between paired thermophilic and mesophilic homologues to evaluate adaptations under the selective pressure of high temperature. We find the residue clusters in thermophilic enzymes generally display improved atomic packing compared to mesophilic enzymes, in agreement with previous research. Unlike residue clusters from mesophilic enzymes, however, thermophilic residue clusters do not have significant cavities. In addition, anchor residues found in many clusters are highly conserved with respect to atomic packing between both thermophilic and mesophilic enzymes. As a result, the improvements in atomic packing observed in thermophilic homologues are not derived from these anchor residues but from neighboring positions, which may serve to expand optimized protein core regions.
 [1] ;  [2] ;  [1] ;  [2] ;  [1] ;  [1]
  1. National Renewable Energy Lab. (NREL), Golden, CO (United States)
  2. Univ. of Colorado, Boulder, CO (United States)
Publication Date:
OSTI Identifier:
Report Number(s):
Journal ID: ISSN 1932-6203
Grant/Contract Number:
Accepted Manuscript
Journal Name:
Additional Journal Information:
Journal Volume: 11; Journal Issue: 1; Related Information: PLoS One; Journal ID: ISSN 1932-6203
Public Library of Science
Research Org:
NREL (National Renewable Energy Laboratory (NREL), Golden, CO (United States))
Sponsoring Org:
USDOE Office of Energy Efficiency and Renewable Energy (EERE), Bioenergy Technologies Office (EE-3B)
Country of Publication:
United States
09 BIOMASS FUELS; 59 BASIC BIOLOGICAL SCIENCES thermophilic; mesophilic; enzymes; atomic packing; clusters; sequence motif analysis; enzyme structure; sequence alignment; protein structure comparison; bacillus; dehydrogenases; protein structure databases; protein domains