title: Structural studies of tri-functional human GART.
abstract: Human purine de novo synthesis pathway contains several multi-functional enzymes, one of which, tri-functional GART, contains three enzymatic activities in a single polypeptide chain. We have solved structures of two domains bearing separate catalytic functions: glycinamide ribonucleotide synthetase and aminoimidazole ribonucleotide synthetase. Structures are compared with those of homologous enzymes from prokaryotes and analyzed in terms of the catalytic mechanism. We also report small angle X-ray scattering models for the full-length protein. These models are consistent with the enzyme forming a dimer through the middle domain. The protein has an approximate seesaw geometry where terminal enzyme units display high mobility owing to flexible linker segments. This resilient seesaw shape may facilitate internal substrate/product transfer or forwarding to other enzymes in the pathway.
authors.affiliation: Structural Genomics Consortium, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17177 Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Welin
authors.forename: Jörg Günter
authors.initials: JG
authors.lastname: Grossmann
authors.forename: Susanne
authors.initials: S
authors.lastname: Flodin
authors.forename: Tomas
authors.initials: T
authors.lastname: Nyman
authors.forename: Pål
authors.initials: P
authors.lastname: Stenmark
authors.forename: Lionel
authors.initials: L
authors.lastname: Trésaugues
authors.forename: Tetyana
authors.initials: T
authors.lastname: Kotenyova
authors.forename: Ida
authors.initials: I
authors.lastname: Johansson
authors.forename: Pär
authors.initials: P
authors.lastname: Nordlund
authors.forename: Lari
authors.initials: L
authors.lastname: Lehtiö
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D001665:Binding Sites; D019731:Carbon-Nitrogen Ligases / Q000737:chemistry*; D020134:Catalytic Domain; D003461:Crystallography; D005998:Glycine / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D051026:Phosphoribosylglycinamide Formyltransferase / Q000737:chemistry*; D020836:Protein Structure, Quaternary; D012267:Ribosemonophosphates / Q000737:chemistry; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
chemical_list: D012267:Ribosemonophosphates; C008891:phosphoribosylamine; D000255:Adenosine Triphosphate; D051026:Phosphoribosylglycinamide Formyltransferase; D019731:Carbon-Nitrogen Ligases; C494823:GART protein, human; D005998:Glycine