Prodrug activation by Cryptosporidium thymidine kinase

Xin Sun, a Biochemistry grad student from the Hedstrom Lab, discusses her recent paper in J. Biol. Chem.:

I get to say the word “diarrhea” within the first 1-2 sentences of
talking to a stranger about what I work on, and the look I get back is always amusing. We work on developing inhibitors against a human pathogen called Cryptosporidium parvum, a nasty little parasite that causes the aforementioned diarrhea. We specifically zoomed in on the parasite’s nucleotide synthesis pathways to look for potential drug targets. Our recent paper looked at the enyzme thymidine kinase from the parasite, and studied its role in activating a prodrug that we showed to be effective in reducing parasite load in both a cell culture assay,  and in a mouse model.

Chloride channels and antiport mechanism

In a new paper in Journal of General Physiology, Brandeis postdoc Hyun-Ho Lim and Professor Christopher Miller examine the detailed mechanism by which a chloride transporter protein works. In particular, this protein does a rather crazy thing: it stoichiometrically swaps a proton on one side of the membrane for two Cl- ions on the other, and countertransports them across the membrane.  In this work, the authors identify a special glutamate residue on the cytoplasmic side of the protein that is responsible for picking up protons on that side in order to carry out this “antiport” mechanism.  (That glutamate is indicated by the spacefilled residue with red oxygen atoms in this depiction of the dimeric protein.)

Actin "pointers" for EM labeling

Single particle electron microscopy reconstruction can be a powerful tool for determining the structure of large protein complexes. One limitation of the technique is the difficulty in coming up with specific labels for the protein that can be visualized with EM. In a new paper in RNA, postdoc Beth Stroupe and coworkers show that the use of the actin-nucleating protein Spire as a cloneable tag allows them to nucleate actin filaments that then “point” to the location of the tag in the complex seen in EM, and applied the technique to their studies of the C complex spliceosome.

Structural diversity of amyloid fibrils

Amyloid fibrils are associated with Alzheimer’s disease. In a recent study published in J. Mol. Biol., Nikolaus Grigorieff and coworkers used electron cyro-microscopy to study these structures and show that these fibrils coexisting in solution can be extremely polymorphic.

Multiple loops in DNA-protein binding complexes

Recent results from the Gelles lab published in PLoS Biology show that lac repressor bound to DNA can form different loop structures and that there are rapid transitions between the structures.

Gabbay Award

On Monday, Nov 10, Prof. Alfred Goldberg from Harvard Medical School will be on campus to receive the 2008 Jacob Heskel Gabbay Award and to deliver a lecture on the topic “Functions of the proteasome from protein degradation and immune surveillance to cancer therapy”

For more information, see the online exhibit at

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