Crystal structure of the essential Mycobacterium tuberculosis phosphopantetheinyl transferase PptT, solved as a fusion protein with maltose binding protein

J Struct Biol. 2014 Dec;188(3):274-8. doi: 10.1016/j.jsb.2014.10.004. Epub 2014 Oct 18.


Phosphopantetheinyl transferases (PPTases) are key enzymes in the assembly-line production of complex molecules such as fatty acids, polyketides and polypeptides, where they activate acyl or peptidyl carrier proteins, transferring a 4'-phosphopantetheinyl moiety from coenzyme A (CoA) to a reactive serine residue on the carrier protein. The human pathogen Mycobacterium tuberculosis encodes two PPTases, both essential and therefore attractive drug targets. We report the structure of the type-II PPTase PptT, obtained from crystals of a fusion protein with maltose binding protein. The structure, at 1.75Å resolution (R=0.156, Rfree=0.191), reveals an α/β fold broadly similar to other type-II PPTases, but with differences in peripheral structural elements. A bound CoA is clearly defined with its pantetheinyl arm tucked into a hydrophobic pocket. Interactions involving the CoA diphosphate, bound Mg(2+) and three active site acidic side chains suggest a plausible pathway for proton transfer during catalysis.

Keywords: Acyl carrier protein; Crystal structure; MBP fusion protein; Mycobacterium tuberculosis; Phosphopantetheinyl transferase type-II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / metabolism*
  • Crystallography, X-Ray
  • Maltose-Binding Proteins / metabolism*
  • Mycobacterium tuberculosis / metabolism*
  • Protein Structure, Secondary
  • Transferases (Other Substituted Phosphate Groups) / metabolism*


  • Bacterial Proteins
  • Maltose-Binding Proteins
  • phosphopantetheinyl transferase
  • Transferases (Other Substituted Phosphate Groups)

Associated data

  • PDB/4QVH