Discrimination of thermophilic and mesophilic proteins

Abstract

Background: There is a considerable literature on the source of the thermostability of proteins from thermophilic organisms. Understanding the mechanisms for this thermostability would provide insights into proteins generally and permit the design of synthetic hyperstable biocatalysts.Results: We have systematically tested a large number of sequence and structure derived quantities for their ability to discriminate thermostable proteins from their non-thermostable orthologs using sets of mesophile-thermophile ortholog pairs. Most of the quantities tested correspond to properties previously reported to be associated with thermostability. Many of the structure related properties were derived from the Delaunay tessellation of protein structures. Conclusions: Carefully selected sequence based indices discriminate better than purely structure based indices. Combined sequence and structure based indices improve performance somewhat further. Based on our analysis, the strongest contributors to thermostability are an increase in ion pairs on the protein surface and a more strongly hydrophobic interior.

Proteome-wide Analysis of Protein Thermal Stability in the Model Higher Plant Arabidopsis thaliana

“…Correlation with Protein Properties-Significant past effort has gone into discovering determinants of protein thermostability, defined herein as the relative ability of a protein to maintain a native conformation under increasing temperature. For the most part, this past work has focused on comparing protein structure (1°and higher-level) between orthologs from mesophilic, thermophilic, and hyperthermophilic prokaryotes (25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40). In some cases a small number of experimental T m s were known (for example, taken from the ProTherm database) (32,37,40), but often it has been assumed that characteristics that differentiate mesophilic from thermophilic primary protein sequences would also be general determinants of thermostability, justifying purely in silico approaches on sequenced genomes (28,29,38) species (17) and found correlations between a number of chemical and structural characteristics of proteins and their relative degree of thermostability.…”

Molecular Determinants of Enzyme Cold Adaptation: Comparative Structural and Computational Studies of Cold- and Warm-Adapted Enzymes

“…The stability of a protein results from a delicate balance between different weak intramolecular interactions. Electrostatic interactions and in particular charge-charge interactions have been shown to play a crucial role in determining protein stability [188]. Charge-charge interactions have distal effects and occur between charged protein groups, even if they are located several angstroms apart.…”

Structural and thermodynamic insight into phenylalanine hydroxylase from the human pathogen Legionella pneumophila

“…But when analyzing the amino acid sequence, the high Arg/(Arg + Lys) ratio (0.67/0.39/0.61/0.44 in lp/cp/cv/hPAH), the low number of Gly residues (10/13/14/15 in lp/cp/cv/hPAH) and the Pro content (14/12/14/12 in lp/cp/cv/hPAH), might all contribute to the thermostability in lpPAH compared to other PAHs, as inferred from comparative analyses of thermophilic proteins versus mesophilic and psychrophilic orthologs aiming to reveal mechanisms of temperature adaptation [15,30]. While arginine residues appear to be superior to lysines to withstand high temperatures, fewer glycines and additional prolines are associated to a reduction in conformational flexibility [30–33].…”