title: Tolerance of point substitution of methionine for isoleucine in hen egg white lysozyme.
abstract: X-ray structure determination of proteins by using the multiple-wavelength anomalous dispersion method targeting selenomethionine is now widely employed. Isoleucine was examined for the second choice of the substitution of methionine next to leucine. We performed a systematic mutational study of the substitutions of methionine for isoleucine. All mutated lysozymes were less stable than the wild-type by about 1 kcal/mol and it is suggested that this instability was caused by the change in residual hydrophobicity from isoleucine to methionine. The X-ray structures of all mutant lysozymes were very similar to that of the wild-type. In addition, both the accessible surface areas and the conformation of the side chain of methionine in all mutant lysozymes were similar to those of the side chain at the respective isoleucine in the wild-type. Therefore, it is suggested that the mutation from isoleucine to methionine in a protein can be considered as a "safe" substitution.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohmura
authors.forename: T
authors.initials: T
authors.lastname: Ueda
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: T
authors.initials: T
authors.lastname: Imoto
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002645:Chickens; D018360:Crystallography, X-Ray; D004355:Drug Stability; D004527:Egg Proteins / Q000737:chemistry / Q000235:genetics; D005260:Female; D007532:Isoleucine / Q000494:pharmacology; D008715:Methionine; D015394:Molecular Structure; D009113:Muramidase / Q000737:chemistry* / Q000235:genetics; D017354:Point Mutation; D011487:Protein Conformation / Q000187:drug effects
chemical_list: D004527:Egg Proteins; D007532:Isoleucine; D008715:Methionine; C421864:hen egg lysozyme; D009113:Muramidase