title: Comparing Residue Clusters from Thermophilic and Mesophilic Enzymes Reveals Adaptive Mechanisms.
abstract: 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. Thus 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.
authors.affiliation: Biosciences Center, National Renewable Energy Laboratory, Golden, Colorado, 80401, United States of America.
authors.forename: Deanne W
authors.initials: DW
authors.lastname: Sammond
authors.affiliation: Department of Chemistry & Biochemistry and the BioFrontiers Institute, University of Colorado, Boulder, Colorado, 80309, United States of America.
authors.forename: Noah
authors.initials: N
authors.lastname: Kastelowitz
authors.affiliation: Biosciences Center, National Renewable Energy Laboratory, Golden, Colorado, 80401, United States of America.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Himmel
authors.affiliation: Department of Chemistry & Biochemistry and the BioFrontiers Institute, University of Colorado, Boulder, Colorado, 80309, United States of America.
authors.forename: Hang
authors.initials: H
authors.lastname: Yin
authors.affiliation: Biosciences Center, National Renewable Energy Laboratory, Golden, Colorado, 80401, United States of America.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Crowley
authors.affiliation: Biosciences Center, National Renewable Energy Laboratory, Golden, Colorado, 80401, United States of America.
authors.forename: Yannick J
authors.initials: YJ
authors.lastname: Bomble
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D000626:Aminopeptidases / Q000737:chemistry; D001105:Archaea / Q000737:chemistry / Q000201:enzymology; D019843:Archaeal Proteins / Q000737:chemistry*; D001419:Bacteria / Q000737:chemistry / Q000201:enzymology; D001426:Bacterial Proteins / Q000737:chemistry*; D016000:Cluster Analysis; D005656:Fungal Proteins / Q000737:chemistry*; D005658:Fungi / Q000737:chemistry / Q000201:enzymology; D006358:Hot Temperature; D007770:L-Lactate Dehydrogenase / Q000737:chemistry; D008291:Malate Dehydrogenase / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D000596:Amino Acids; D019843:Archaeal Proteins; D001426:Bacterial Proteins; D005656:Fungal Proteins; D007770:L-Lactate Dehydrogenase; D008291:Malate Dehydrogenase; D000626:Aminopeptidases