title: Conformational Changes in the tryptophan synthase from a hyperthermophile upon alpha2beta2 complex formation: crystal structure of the complex.
abstract: The three-dimensional structure of the bifunctional tryptophan synthase alpha(2)beta(2) complex from Pyrococcus furiosus was determined by crystallographic analysis. This crystal structure, with the structures of an alpha subunit monomer and a beta(2) subunit dimer that have already been reported, is the first structural set in which changes in structure that occur upon the association of the individual tryptophan synthase subunits were observed. To elucidate the structural basis of the stimulation of the enzymatic activity of each of the alpha and beta(2) subunits upon alpha(2)beta(2) complex formation, the conformational changes due to complex formation were analyzed in detail compared with the structures of the alpha monomer and beta(2) subunit dimer. The major conformational changes due to complex formation occurred in the region correlated with the catalytic function of the enzyme as follows. (1) Structural changes in the beta subunit were greater than those in the alpha subunit. (2) Large movements of A46 and L165 in the alpha subunit due to complex formation caused a more open conformation favoring the entry of the substrate at the alpha active site. (3) The major changes in the beta subunit were the broadening of a long tunnel through which the alpha subunit product (indole) is transferred to the beta active site and the opening of an entrance at the beta active site. (4) The changes in the conformations of both the alpha and beta subunits due to complex formation contributed to the stabilization of the subunit association, which is critical for the stimulation of the enzymatic activities.
authors.affiliation: Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Soo Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ogasahara
authors.forename: Jichun
authors.initials: J
authors.lastname: Ma
authors.forename: Kazuya
authors.initials: K
authors.lastname: Nishio
authors.forename: Masami
authors.initials: M
authors.lastname: Ishida
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Yamagata
authors.forename: Tomitake
authors.initials: T
authors.lastname: Tsukihara
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Yutani
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D046911:Macromolecular Substances; D008958:Models, Molecular; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry; D020027:Pyrococcus furiosus / Q000201:enzymology*; D014367:Tryptophan Synthase / Q000737:chemistry* / Q000378:metabolism
chemical_list: D046911:Macromolecular Substances; D021122:Protein Subunits; D014367:Tryptophan Synthase