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My favorite enzymes, part 1: S-adenosylmethionine decarboxylase from Trypanosoma brucei

August 28, 2010

For me, a highlight of the recent ICOPA XII conference was getting to hear Meg Phillips talk about her work on S-adenosylmethionine decarboxylase (EC 4.1.1.50) in Trypanosoma brucei. This enzyme is a part of the polyamine synthesis pathway and, as such, might be a good one to target in the treatment of African sleeping sickness.

When Meg’s lab started to characterize the T. brucei AdoMetDC in vitro, they found that its activity was only about 1/300 of that the human enzyme. If I had been doing this study, I might have assumed simply that the assay conditions were somehow ill-suited to the T. brucei enzyme. But Meg’s group dug deeper — much deeper. They found that, in addition to the normal gene for AdoMetDC in the T. brucei genome, there was a second AdoMetDC-like gene. This gene codes for a “prozyme” that is not itself catalytically active, but that binds to the “real” AdoMetDC and allosterically activates it, boosting its activity by 1,200-fold. Thus, in live T. brucei cells, the two polypeptides active form a highly unusual but highly effective heterodimer. Even after hearing this story a couple of times, I remain amazed that Meg’s lab figured it out.

[Reference: E. K. Willert, R. Fitzpatrick, and M. A. Phillips (2007). Allosteric regulation of an essential trypanosome polyamine biosynthetic enzyme by a catalytically dead homolog. PNAS 104: 8075-80.]

One comment

  1. […] blog. They have nothing to do with music, but feel free to read them anyway! Here are the links: * My favorite enzymes, part 1: S-adenosylmethionine decarboxylase from Trypanosoma brucei * My favorite enzymes, parts 2 and 3 * My favorite enzymes, part 4: […]



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