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

Biochemistry. 2010 May 18;49(19):4159-68. doi: 10.1021/bi100150v.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / chemistry
  • Adenosine Diphosphate / metabolism
  • Amino Acid Sequence
  • Binding Sites
  • Catalysis
  • Crystallography, X-Ray
  • Glycopeptides / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Substrate Specificity
  • Sulfotransferases / chemistry*
  • Sulfotransferases / metabolism*
  • Teicoplanin / analogs & derivatives*
  • Teicoplanin / chemistry
  • Teicoplanin / metabolism

Substances

  • Glycopeptides
  • Teicoplanin
  • Adenosine Diphosphate
  • teicoplanin aglycone
  • adenosine 3'-phosphate-5'-phosphate
  • Sulfotransferases