This month on the PDB: December

Hi everybody! 162 structures were released from November 28th to December 5th, ranging from the typical Homo sapiens proteins to the zesty proteins of the Asian rice. Without further ado, let us take some time to peruse this newly released selection of never-before seen macromolecule structures!

  1. HSP90 WITH [sic] indazole derivative, by Graedler, U., Amaral, M., & Schuetz, D.. You know how part of what makes the PDB exciting is that the PDB releases never-before-seen-structures? Well this is not one such case, but just like the lysozymes of last week, this title is notable in that it is actually the name of not one, but SIX separate releases for this week. Hsp90 (heat shock protein 90) is a chaperone protein that promotes the proper folding, stabilization, and activation of a client polypeptide in an ATP-dependent manner, commonly as a dimer. In teaching materials, Hsp90 usually looks like some weird ellipses lumped together to form some two-pronged rabbit head-looking thing, but now you can see what it really looks like, in six slightly different conformations! Indazole derivatives are Hsp90 inhibitors, and these monomeric structures of human Hsp90 are each binding a slightly different indazole derivative. Why are they monomeric and what’s with all these different indazole derivatives? Well, the paper hasn’t been published yet so you’ll have to keep on guessing for a while, but until then, you can entertain yourself by looking at the structures. The PDB accession codes are 5LNY, 5LNZ, 5LO0, 5LO1, 5LO5, and 5LO6. The following figure includes an approximate surface density of the protein, which is why it probably looks a little strange. You can see there are slight differences in conformation between the structures, but for the most part they look decently similar.3.1
  2. Crystal structure of Os79 from O. sativa in complex with UDP, by Wetterhorn, K.M., Gabardi, K., Michlmayr, H., Malachova, A., Busman, M., McCormick, S.P., Berthiller, F., Adam, G., and Rayment, I. This is actually a generalization of the titles of four different structures, all of Os79 from O. sativa in complex with UDP, with and without different mutations and some with different sugar moieties. Oryza sativa, the humble Asian rice, one of the most essential cereal crops to society, is susceptible to head blight infections caused by fungi in the Fusarium genus that affects many other cereal crops as well. Trichothecene toxins are a family of toxins that are responsible for the virulence of Fusarium head blight, and toxic to humans and livestock as well as plants since it inhibits protein synthesis in the eukaryotic ribosome. Os79 is a UDP-glycosyltransferase: it adds a glycosyl moiety to a substrate using a co-substrate such as a UDP-glucose (a glucose bound to a uridine diphosphate). Glycosylating trichothecenes reduces its bioavailability and toxicity, so it would be super rad to engineer a protein that could easily glycosylate these toxins and prevent humanity from losing a lot of crops, some livestock, and a few humans every year. That’s a lot of lives saved! Os79 seems to be a good candidate for this ^type of protein engineering, but this goal is still in the fledgling stages as there are a lot of different trichothecenes and only one Os79 (Remember that enzyme-substrate specificity which we thought made enzymes so cool? Well now it’s sort of biting us in the butt. Enzymes are still cool though, obviously). The good news is that the group that released these structures also did some structural and activity analyses and determined what parts of the structure controlled its specificity. You can read all about it here: http://pubs.acs.org.proxy3.library.mcgill.ca/doi/pdf/10.1021/acs.biochem.7b01007. The PDB accession codes are 6BK0, 6BK1, 6BK2, and 6BK3.3.2

Someone requested the experimental method metrics of the PDB releases, so here they are: out of 162 structures released this week, 146 were obtained through x-ray diffraction. 4 structures were obtained using cryo-electron microscopy, the up-and-coming technology in the world of structural biology (the 2017 Nobel Prize in Chemistry was awarded to the developers of cryo-EM), a lower number than the usual. This week, there are a whopping 12 structures obtained through solution microscopy. What are these mysterious 12 structures? The 4 cryo-EM structures? The 144 x-ray diffraction structures? (You already saw 2 of them.) Go check them out yourself on this week’s PDB release! You can find it here: https://www.rcsb.org/pdb/results/results.do?tabtoshow=Current&qrid=9D74214C. Happy lurking!

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