title: Common structural elements in the architecture of the cofactor-binding domains in unrelated families of pyridoxal phosphate-dependent enzymes.
abstract: A detailed comparison of the structures of aspartate aminotransferase, alanine race-mase, the beta subunit of tryptophan synthase, D-amino acid aminotransferase and glycogen phosphorylase has revealed more extensive structural similarities among pyridoxal phosphate (PLP)-binding domains in these enzymes than was observed previously. These similarities consist of seven common structural segments of the polypeptide chain, which form an extensive common structural organization of the backbone chain responsible for the appropriate disposition of key residues, some from the aligned fragments and some from variable loops joined to these fragments, interacting with PLPs in these enzymes. This common structural organization contains an analogous hydrophobic minicore formed from four amino acid side chains present in the two most conserved structural elements. In addition, equivalent alpha-beta-alpha-beta supersecondary structures are formed by these seven fragments in three of the five structures: alanine racemase, tryptophan synthase and glycogen phosphorylase. Despite these similarities, it is generally accepted that these proteins do not share a common heritage, but have arisen on five separate occasions. The common and contiguous alpha-beta-alpha-beta structure accounts for only 28 residues and all five enzymes differ greatly in both the orientation of the PLP pyridoxal rings and their contacts with residues close to the common structural elements.
authors.affiliation: Department of Biochemistry and Pharmacy, Turku Centre for Biotechnology, Abo Akademi University, Finland.
authors.forename: K A
authors.initials: KA
authors.lastname: Denessiouk
authors.forename: A I
authors.initials: AI
authors.lastname: Denesyuk
authors.forename: J V
authors.initials: JV
authors.lastname: Lehtonen
authors.forename: T
authors.initials: T
authors.lastname: Korpela
authors.forename: M S
authors.initials: MS
authors.lastname: Johnson
mesh_terms: D000411:Alanine Racemase / Q000737:chemistry / Q000378:metabolism; D000410:Alanine Transaminase / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D003198:Computer Simulation; D051263:D-Alanine Transaminase; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D006005:Phosphorylases / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D011732:Pyridoxal Phosphate / Q000378:metabolism*; D011817:Rabbits; D014367:Tryptophan Synthase / Q000737:chemistry / Q000378:metabolism
chemical_list: D004798:Enzymes; D011732:Pyridoxal Phosphate; D006005:Phosphorylases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D051263:D-Alanine Transaminase; D014367:Tryptophan Synthase; D000411:Alanine Racemase