title: Enzymes with molecular tunnels.
abstract: As a result of recent advances in molecular cloning, protein expression, and X-ray crystallography, it has now become feasible to examine complicated protein structures at high resolution. For those enzymes with multiple catalytic sites, a common theme is beginning to emerge; the existence of molecular tunnels that connect one active site with another. The apparent mechanistic advantages rendered by these molecular conduits include the protection of unstable intermediates and an improvement in catalytic efficiency by blocking the diffusion of intermediates into the bulk solvent. Since the first molecular tunnel within tryptophan synthase was discovered in 1988, tunnels within carbamoyl phosphate synthetase, glutamine phosphoribosylpyrophosphate amidotransferase, asparagine synthetase, glutamate synthase, imidazole glycerol phosphate synthase, glucosamine 6-phosphate synthase, and carbon monoxide dehydrogenase/acetyl-CoA synthase have been identified. The translocation of ammonia, derived from the hydrolysis of glutamine, is the most abundant functional requirement for a protein tunnel identified thus far. Here we describe and summarize our current understanding of molecular tunnels observed in various enzyme systems.
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, Texas 77843-3012, USA.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Raushel
authors.forename: James B
authors.initials: JB
authors.lastname: Thoden
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Holden
mesh_terms: D000619:Aminohydrolases / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D014367:Tryptophan Synthase / Q000737:chemistry / Q000378:metabolism
chemical_list: D004798:Enzymes; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); C087227:imidazole glycerol phosphate synthase; D000619:Aminohydrolases; D014367:Tryptophan Synthase