title: Nonneutral evolution of volume fluctuations in lysozymes revealed by normal-mode analysis of compressibility.
abstract: The evolution of structural fluctuations of proteins was examined by calculating the isothermal compressibility (β(T)) values of chicken lysozyme and its six evolutionary mutants at Thr40, Ile55, and Ser91 (a ternary mutant corresponding to bobwhite lysozyme) from their X-ray structures by normal-mode analysis at 300 K. The β(T) values of the two extant lysozymes from chicken and bobwhite were 1.61 and 1.59 Mbar(-1), respectively, but five other evolutionary mutants showed larger β(T) values of up to 2.17 Mbar(-1). These results suggest that ancestral lysozymes exhibit larger volume fluctuations than extant ones, and hence that the molecular evolution of lysozymes has followed a nonneutral evolutionary pathway. The evolutionary mutants contained large amount of cavities, although no change was visible in the X-ray structures. There was a linear correlation between β(T) and total cavity volume, predicting that the cavity volume or atomic packing is an important factor regulating volume fluctuations during the molecular evolution of this protein.
authors.affiliation: Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Kagamiyama, Higashi-Hiroshima, Japan.
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Mimura
authors.forename: Takahisa
authors.initials: T
authors.lastname: Yamato
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kamiyama
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Gekko
mesh_terms: D000818:Animals; D002645:Chickens; D019143:Evolution, Molecular; D008247:Lysosomes / Q000737:chemistry / Q000201:enzymology*; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D009113:Muramidase