title: Additivity in both thermodynamic stability and thermal transition temperature for rubredoxin chimeras via hybrid native partitioning.
abstract: Given any operational definition of pairwise interaction, the set of residues that differ between two structurally homologous proteins can be uniquely partitioned into subsets of clusters for which no such interactions occur between clusters. Although hybrid protein sequences that preserve such clustering are consistent with tertiary structures composed of only parental native-like interactions, the stability of such predicted structures will depend upon the physical robustness of the assumed interaction potential. A simple distance cutoff criterion was applied to the most thermostable protein known to predict such a seven-residue cluster in the metal binding site region of Pyrococcus furiosus rubredoxin and a mesophile homolog. Both conformational stability and thermal transition temperature measurements demonstrate that 39% of the differential stability arises from these seven residues.
authors.affiliation: Wadsworth Center, New York State Department of Health, Empire State Plaza, Albany, New York 12201, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: LeMaster
authors.forename: Griselda
authors.initials: G
authors.lastname: Hernández
mesh_terms: D001665:Binding Sites; D003013:Clostridium / Q000235:genetics / Q000378:metabolism; D004795:Enzyme Stability / Q000502:physiology; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D006358:Hot Temperature; D008279:Magnetic Resonance Imaging; D017434:Protein Structure, Tertiary; D020027:Pyrococcus furiosus / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D016914:Ribonuclease H / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012416:Rubredoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013816:Thermodynamics; D016963:Thermus thermophilus / Q000201:enzymology / Q000235:genetics
chemical_list: D011993:Recombinant Fusion Proteins; D012416:Rubredoxins; D016914:Ribonuclease H