Steve Ealick's Research Group
Burkholderia glumae ToxA
Toxoflavin is a major virulence factor of the rice pathogen Burkholderia glumae. The tox operon of B. glumae contains five putative toxoflavin biosynthetic genes toxABCDE. ToxA is a predicted S-adenosylmethionine dependent methyltransferase and toxA knockouts of B. glumae are less virulent in plant infection models. Here we show that ToxA performs two consecutive methylations to convert the putative azapteridine intermediate, 1,6-didemethyltoxoflavin, to toxoflavin. Our crystal structures of complexes reveal the molecular basis of the dual methyltransferase activity.
The structure of ToxA contains a Class I methyltransferase fold having an N-terminal extension that either closes over the active site or is largely disordered.
|Apo ToxA forms a homodimer having noncrystallographic twofold symmetry (top). In contrast, ligands interfere with homodimer formation, so the structures of complexes tend to be monomeric.|
Toxoflavin binds in a deep slot between the Class I methyltransferase domain and the flap domain.
Fenwick MK, Philmus B, Begley TP, and Ealick SE. Burkholderia glumae ToxA is a Dual Specificity Methyltransferase that Catalyzes the Last Two Steps of Toxoflavin Biosynthesis. Biochemistry 55:2748-2759 (2016).