title: Crystal structures of the glycopeptide sulfotransferase Teg12 in a complex with the teicoplanin aglycone.
abstract: The TEG gene cluster, a glycopeptide biosynthetic gene cluster that is predicted to encode the biosynthesis of a polysulfated glycopeptide congener, was recently cloned from DNA extracted directly from desert soil. This predicted glycopeptide gene cluster contains three closely related sulfotransferases (Teg12, -13, and -14) that sulfate teicoplanin-like glycopeptides at three unique sites. Here we report a series of structures: an apo structure of Teg12, Teg12 bound to the desulfated cosubstrate 3'-phosphoadenosine 5'-phosphate, and Teg12 bound to the teicoplanin aglycone. Teg12 appears to undergo a series of significant conformational rearrangements during glycopeptide recruitment, binding, and catalysis. Loop regions that exhibit the most conformational flexibility show the least sequence conservation between TEG sulfotransferases. Site-directed mutagenesis guided by our structural studies confirmed the importance of key catalytic residues as well as the importance of residues found throughout the conformationally flexible loop regions.
authors.affiliation: Howard Hughes Medical Institute, Laboratory of Genetically Encoded Small Molecules, Laboratory of Molecular Biophysics, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Bick
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Banik
authors.forename: Seth A
authors.initials: SA
authors.lastname: Darst
authors.forename: Sean F
authors.initials: SF
authors.lastname: Brady
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D006020:Glycopeptides / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000737:chemistry* / Q000378:metabolism*; D017334:Teicoplanin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
chemical_list: D006020:Glycopeptides; D017334:Teicoplanin; D000244:Adenosine Diphosphate; C063101:teicoplanin aglycone; C010840:adenosine 3'-phosphate-5'-phosphate; D015238:Sulfotransferases