Geschmack ist vorhersagbar: Mit FlavorMiner. FlavorMiner heißt das Tool, das IPB-Chemiker und Partner aus Kolumbien jüngst entwickelt haben. Das Programm kann, basierend auf maschinellem Lernen (KI), anhand der…
Seit Februar 2021 bietet Wolfgang Brandt, ehemaliger Leiter der Arbeitsgruppe Computerchemie am IPB, sein Citizen Science-Projekt zur Pilzbestimmung an. Dafür hat er in regelmäßigen Abständen öffentliche Vorträge zur Vielfalt…
Heuts, D. P. H. M.; Weissenborn, M. J.; Olkhov, R. V.; Shaw, A. M.; Gummadova, J.; Levy, C.; Scrutton, N. S.;Crystal Structure of a Soluble Form of Human CD73 with Ecto-5′-Nucleotidase ActivityChemBioChem132384-2391(2012)DOI: 10.1002/cbic.201200426
CD73 is a dimeric ecto‐5′‐nucleotidase that is expressed on the exterior side of the plasma membrane. CD73 has important regulatory functions in the extracellular metabolism of certain nucleoside monophosphates, in particular adenosine monophosphate, and has been linked to a number of pathological conditions such as cancer and myocardial ischaemia. Here, we present the crystal structure of a soluble form of human soluble CD73 (sCD73) at 2.2 Å resolution, a truncated form of CD73 that retains ecto‐5′‐nucleotidase activity. With this structure we obtained insight into the dimerisation of CD73, active site architecture, and a sense of secondary modifications of the protein. The crystal structure reveals a conserved loop that is directly involved in the dimer‐dimer interaction showing that the two subunits of the dimer are not linked by disulfide bridges. Using biophotonic microarray imaging we were able to confirm glycosylation of the enzyme and show that the enzyme is decorated with a variety of oligosaccharide structures. The crystal structure of sCD73 will aid the design of inhibitors or activator molecules for the treatment of several diseases and prove useful in explaining the possible roles of single nucleotide polymorphisms in physiology and disease.
Publikation
Parthier, C.; Görlich, S.; Jaenecke, F.; Breithaupt, C.; Bräuer, U.; Fandrich, U.; Clausnitzer, D.; Wehmeier, U. F.; Böttcher, C.; Scheel, D.; Stubbs, M. T.;The O-Carbamoyltransferase TobZ Catalyzes an Ancient Enzymatic ReactionAngew. Chem. Int. Ed.514046-4052(2012)DOI: 10.1002/anie.201108896
An ancient reaction vessel: TobZ carbamoylates the antibiotic tobramycin to form nebramycin 5′. The YrdC‐like domain (blue) catalyzes the formation of the novel intermediate carbamoyladenylate, which is channeled through a common “reaction chamber” to the Kae1‐like domain (brown), site of carbamoyl transfer.
Publikation
van Berkel, S. S.; Brauch, S.; Gabriel, L.; Henze, M.; Stark, S.; Vasilev, D.; Wessjohann, L. A.; Abbas, M.; Westermann, B.;Traceless Tosylhydrazone-Based Triazole Formation: A Metal-Free Alternative to Strain-Promoted Azide-Alkyne CycloadditionAngew. Chem. Int. Ed.515343-5346(2012)DOI: 10.1002/anie.201108850
Triple‐T trick! Traceless tosylhydrazone‐based triazole formation is readily achieved by reacting primary amines with functional α,α‐dichlorotosylhydrozones under ambient conditions. This fast and efficient alternative affords exclusively 1,4‐substituted triazole “click products” with complete retention of configuration. Primary amines, inherent to many natural products, can be modified in this way without protecting group manipulations.