title: Crystal structure of two quaternary complexes of dethiobiotin synthetase, enzyme-MgADP-AlF3-diaminopelargonic acid and enzyme-MgADP-dethiobiotin-phosphate; implications for catalysis.
abstract: The crystal structures of two complexes of dethiobiotin synthetase, enzyme-diaminopelargonic acid-MgADP-AlF3 and enzyme-dethiobiotin-MgADP-Pi, respectively, have been determined to 1.8 A resolution. In dethiobiotin synthetase, AlF3 together with carbamylated diaminopelargonic acid mimics the phosphorylated reaction intermediate rather than the transition state complex for phosphoryl transfer. Observed differences in the binding of substrate, diaminopelargonic acid, and the product, dethiobiotin, suggest considerable displacements of substrate atoms during the ring closure step of the catalytic reaction. In both complexes, two metal ions are observed at the active site, providing evidence for a two-metal mechanism for this enzyme.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Käck
authors.forename: J
authors.initials: J
authors.lastname: Sandmark
authors.forename: K J
authors.initials: KJ
authors.lastname: Gibson
authors.forename: G
authors.initials: G
authors.lastname: Schneider
authors.forename: Y
authors.initials: Y
authors.lastname: Lindqvist
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism*; D017607:Aluminum Compounds / Q000737:chemistry / Q000378:metabolism; D000599:Amino Acids, Diamino / Q000737:chemistry / Q000378:metabolism; D001710:Biotin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D019731:Carbon-Nitrogen Ligases / Q000737:chemistry* / Q000378:metabolism*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D005459:Fluorides / Q000737:chemistry / Q000378:metabolism; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010710:Phosphates / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011487:Protein Conformation
chemical_list: D017607:Aluminum Compounds; D000599:Amino Acids, Diamino; D010710:Phosphates; C004720:7,8-diaminopelargonic acid; D000244:Adenosine Diphosphate; D001710:Biotin; C004749:desthiobiotin; D019731:Carbon-Nitrogen Ligases; C020024:dethiobiotin synthetase; D008274:Magnesium; D005459:Fluorides; C032311:aluminum fluoride