Crystal structures of the glycopeptide sulfotransferase Teg12 in a complex with the teicoplanin aglycone.

Publication Type:

Journal Article


Biochemistry, Volume 49, Issue 19, p.4159-68 (2010)


Adenosine Diphosphate, Amino Acid Sequence, Binding Sites, Catalysis, Crystallography, X-Ray, Glycopeptides, Models, Molecular, Molecular Sequence Data, Protein Conformation, Substrate Specificity, Sulfotransferases, Teicoplanin


<p>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.</p>