title: Structural analysis of two enzymes catalysing reverse metabolic reactions implies common ancestry.
abstract: The crystal structure of the dimeric anthranilate phosphoribosyltransferase (AnPRT) reveals a new category of phosphoribosyltransferases, designated as class III. The active site of this enzyme is located within the flexible hinge region of its two-domain structure. The pyrophosphate moiety of phosphoribosylpyrophosphate is co-ordinated by a metal ion and is bound by two conserved loop regions within this hinge region. With the structure of AnPRT available, structural analysis of all enzymatic activities of the tryptophan biosynthesis pathway is complete, thereby connecting the evolution of its enzyme members to the general development of metabolic processes. Its structure reveals it to have the same fold, topology, active site location and type of association as class II nucleoside phosphorylases. At the level of sequences, this relationship is mirrored by 13 structurally invariant residues common to both enzyme families. Taken together, these data imply common ancestry of enzymes catalysing reverse biological processes--the ribosylation and deribosylation of metabolic pathway intermediates. These relationships establish new links for enzymes involved in nucleotide and amino acid metabolism.
authors.affiliation: EMBL Hamburg Outstation c/o DESY, Notkestrasse 85, D-22603 Hamburg, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Mayans
authors.forename: Andreas
authors.initials: A
authors.lastname: Ivens
authors.forename: L Johan
authors.initials: LJ
authors.lastname: Nissen
authors.forename: Kasper
authors.initials: K
authors.lastname: Kirschner
authors.forename: Matthias
authors.initials: M
authors.lastname: Wilmanns
mesh_terms: D000595:Amino Acid Sequence; D000877:Anthranilate Phosphoribosyltransferase / Q000737:chemistry* / Q000235:genetics; D019843:Archaeal Proteins / Q000737:chemistry / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D001665:Binding Sites; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000737:chemistry; D019143:Evolution, Molecular; D001411:Geobacillus stearothermophilus / Q000201:enzymology; D008274:Magnesium / Q000378:metabolism; D008969:Molecular Sequence Data; D010430:Pentosyltransferases / Q000737:chemistry* / Q000145:classification* / Q000235:genetics; D017434:Protein Structure, Tertiary; D057845:Pyrimidine Phosphorylases; D016415:Sequence Alignment; D013045:Species Specificity; D016944:Sulfolobus / Q000201:enzymology; D013939:Thymidine Phosphorylase / Q000737:chemistry; D014364:Tryptophan / Q000096:biosynthesis
chemical_list: D019843:Archaeal Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D014364:Tryptophan; D010430:Pentosyltransferases; D057845:Pyrimidine Phosphorylases; D000877:Anthranilate Phosphoribosyltransferase; D013939:Thymidine Phosphorylase; D008274:Magnesium