Octameric Structure of the Human Bifunctional Enzyme PAICS in Purine Biosynthesis

Mammalian amyloidogenic proteins promote prion nucleation in yeast

“…Notably, some of these proteins are known to form multimers, and in a separate experiment employing the ade2 mutant strain, we have specifically shown that the Sup35N-Ade2 and Sup35NM-Ade2 constructs produce functional AIR carboxylase in yeast ( Fig S3D). This confirms that these chimeric proteins form multimeric complexes in yeast, because the functionality of AIR carboxylase depends on its multimerization [36]. Therefore, our data show that the ability of a protein to promote prion nucleation in a fusion to a fragment bearing the PrD of Sup35 depends on the amyloidogenic properties of such a protein, rather than with its ability to form multimeric complexes per se.…”

Structure of SAICAR synthetase from Pyrococcus horikoshii OT3: Insights into thermal stability

“…The first crystal structure was solved from S. cerevisiae (PDBid 1a48; [35]) at a resolution of 1.9Å. Subsequently, several crystal structures of the native and its complex from S. cerevisiae (PDB-ids: 1obg, 1obd, 2cnu, 2cnv and 2cnq), T. maritima (PDB-id: 1kut [36]), E. coli (PDB-ids: 2gqs and 2gqr [37]), G. kaustophilus (PDB-id: 2ywv), M. jannaschii (PDB-ids: 2z02 and 2yzl), E. chaffeensis (PDB-id: 3kre), C. perfringens (PDB-id: 3nua), H. sapiens (PDB-id: 2h31 [38]) and M. abscessus (PDB-id: 3r9r) have been reported. According to the published reports, the enzyme is a monomer in S. cerevisiae, a covalent dimer in T. maritima and a non-covalent dimer in E. coli, while the bifunctional enzyme PAICS in human is an octamer.…”

The GARD platform for potency assessment of skin sensitizing chemicals_suppl

“…In a subsequent step to confirm that our selections of training and test set were unbiased and that the predictive model was not entirely dependent on the composition of the training set, we constructed 18 alternative random forest models, where the composition of chemicals in the training and test set were randomly shuffled. For each new model, we repeated the complete process of variable selection in purine biosynthesis (Lane and Fan, 2015;Li et al, 2007), and TMEM97 (part of GPS) is a regulator of cholesterol levels (Bartz et al, 2009), which is further described to be involved in cell cycle regulation, cell migration and invasion in a glioma cell model according to RNA interference experiments (Qiu et al, 2015). DHCR24 (another GPS transcript) represents a multifunctional enzyme localized to the endoplasmic reticulum (ER) that catalyzes the final step in cholesterol-synthesis (Waterham et al, 2001) but also possesses anti-apoptotic activity as, for example, shown for neuronal cells under ER stress (Lu et al, 2014).…”