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Response of a Protein Structure to Cavity-Creating Mutations and Its Relation to the Hydrophobic Effect

Eriksson, A. E. ; Baase, W. A. ; X.-J. Zhang ; Heinz, D. W. ; Blaber, M. ; Baldwin, E. P. ; Matthews, B. W.

Science (American Association for the Advancement of Science), 1992-01, Vol.255 (5041), p.178-183 [Periódico revisado por pares]

WASHINGTON: American Society for the Advancement of Science

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Título:
Response of a Protein Structure to Cavity-Creating Mutations and Its Relation to the Hydrophobic Effect
Autor: Eriksson, A. E. ; Baase, W. A. ; X.-J. Zhang ; Heinz, D. W. ; Blaber, M. ; Baldwin, E. P. ; Matthews, B. W.
Assuntos: Amino Acid Sequence ; Amino acids ; Atoms ; Biochemistry ; Biological and medical sciences ; Biology ; Calorimetry ; Coordinate systems ; Data collection ; Free energy ; Fundamental and applied biological sciences. Psychology ; Lysozyme ; Melting ; Models, Molecular ; Molecular biophysics ; Molecular Sequence Data ; Multidisciplinary Sciences ; Muramidase - chemistry ; Muramidase - genetics ; Mutagenesis, Site-Directed ; mutants ; Mutation ; Mutation (Biology) ; phage T4 ; Protein Conformation ; Protein stability ; Protein structure ; Proteins ; Research Article ; Science & Technology ; Science & Technology - Other Topics ; Solvents ; Structure ; Structure in molecular biology ; Structure-Activity Relationship ; Surface areas ; T-Phages - enzymology ; T-Phages - genetics ; Thermodynamics ; Tridimensional structure ; X-ray crystallography ; X-Ray Diffraction
É parte de: Science (American Association for the Advancement of Science), 1992-01, Vol.255 (5041), p.178-183
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Descrição: Six "cavity-creating" mutants, Leu$^{46}$ → Ala (L46A), L99A, L118A, L121A, L133A, and Phe$^{153}$ → Ala (F153A), were constructed within the hydrophobic core of phage T4 lysozyme. The substitutions decreased the stability of the protein at pH 3.0 by different amounts, ranging from 2.7 kilocalories per mole (kcal mol$^{-1}$) for L46A and L121A to 5.0 kcal mol$^{-1}$ for L99A. The double mutant L99A/F153A was also constructed and decreased in stability by 8.3 kcal mol$^{-1}$. The x-ray structures of all of the variants were determined at high resolution. In every case, removal of the wild-type side chain allowed some of the surrounding atoms to move toward the vacated space but a cavity always remained, which ranged in volume from 24 cubic angstroms ($\overset{\circ}{\mathrm A}$^3$) for L46A to 150 $\overset{\circ}{\mathrm A}$^3$ for L99A. No solvent molecules were observed in any of these cavities. The destabilization of the mutant Leu → Ala proteins relative to wild type can be approximated by a constant term (∼2.0 kcal mol$^{-1}$) plus a term that increases in proportion to the size of the cavity. The constant term is approximately equal to the transfer free energy of leucine relative to alanine as determined from partitioning between aqueous and organic solvents. The energy term that increases with the size of the cavity can be expressed either in terms of the cavity volume (24 to 33 cal mol$^{-1} \overset{\circ}{\mathrm A}$^{-3}$) or in terms of the cavity surface area (20 cal mol$^{-1} \overset{\circ}{\mathrm A}^{-2}$). The results suggest how to reconcile a number of conflicting reports concerning the strength of the hydrophobic effect in proteins.
Editor: WASHINGTON: American Society for the Advancement of Science
Idioma: Inglês

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Response of a Protein Structure to Cavity-Creating Mutations and Its Relation to the Hydrophobic Effect

Eriksson, A. E. ; Baase, W. A. ; X.-J. Zhang ; Heinz, D. W. ; Blaber, M. ; Baldwin, E. P. ; Matthews, B. W.

WASHINGTON: American Society for the Advancement of Science

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