title: Structure of imidazole glycerol phosphate synthase from Thermus thermophilus HB8: open-closed conformational change and ammonia tunneling.
abstract: Imidazole glycerol phosphate synthase (IGPs) catalyzes the fifth step in the histidine biosynthetic pathway located at the branch point to de novo purine biosynthesis. IGPs is a multienzyme comprising glutaminase and synthase subunits. The glutaminase activity, which hydrolyzes glutamine to give ammonia, is coupled with substrate binding to the synthase subunit. The three-dimensional structure of the IGPs from Thermus thermophilus HB8 has been determined at 2.3 A resolution, and compared with the previously determined structures for the yeast and Thermotoga maritima enzymes. The structure of each subunit is similar to that of the corresponding domain in the yeast enzyme or subunit in the T. maritima enzyme. However, the overall structure is significantly different from the yeast and T. maritima enzymes, indicating that IGPs may change the relative orientation between the two subunits and close the glutaminase site upon glutamine binding. The putative ammonia tunnel, which carries nascent ammonia from glutaminase to the synthase site, has a closed gate comprising a cyclic salt bridge formed by four charged residues of the synthase subunit. The side chain of Lys100 in the cyclic salt bridge might change its side chain direction to form new interactions with the main chain carbonyl group of glutamine from the synthase subunit and the hydoxyl group of tyrosine from the glutaminase subunit, resulting in the opening of the gate for ammonia transfer.
authors.affiliation: Department of Chemistry, Graduate School of Science, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka 558-8585.
authors.forename: Rie
authors.initials: R
authors.lastname: Omi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
authors.forename: Masaru
authors.initials: M
authors.lastname: Goto
authors.forename: Ikuko
authors.initials: I
authors.lastname: Miyahara
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kagamiyama
authors.forename: Ken
authors.initials: K
authors.lastname: Hirotsu
mesh_terms: D000619:Aminohydrolases / Q000737:chemistry* / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D005972:Glutaminase / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016963:Thermus thermophilus / Q000201:enzymology*
chemical_list: D005973:Glutamine; D000641:Ammonia; C087227:imidazole glycerol phosphate synthase; D005972:Glutaminase; D000619:Aminohydrolases