NIH R01 · 2024
Transformylase Enzymes Dihydrofolate Reductase
Project Summary/Abstract Combining isotopic labeling and gas cluster ion beam surface ionization mass spectrometry (GCIB-SIMS), we found the purinosome metabolon consists of nine enzymes that channel phosphoribosyl pyrophosphate to AMP and GMP. The metabolon greatly increases the pathway flux and unexpectedly favors partitioning of IMP to AMP. Chemical imaging of the cell revealed “hot spots” of these metabolites. We presume that these are located at the microtubule/mitochondrion interface based on temporal fluorescent imaging that found a directional movement of the purinosome along the microtubules to the mitochondria. We uncovered two mechanisms that govern purinosome assembly. One…
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