Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5913977 | Journal of Structural Biology | 2014 | 5 Pages |
Abstract
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 4â²-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 1.75Â Ã
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 Mg2+ and three active site acidic side chains suggest a plausible pathway for proton transfer during catalysis.
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Authors
James Jung, Ghader Bashiri, Jodie M. Johnston, Alistair S. Brown, David F. Ackerley, Edward N. Baker,