Reversible compartmentalization of de novo purine biosynthetic complexes in living cells

Songon An, Ravindra Kumar, Erin D. Sheets, Stephen J. Benkovic

Research output: Contribution to journalArticlepeer-review

283 Scopus citations

Abstract

Purines are synthesized de novo in 10 chemical steps that are catalyzed by six enzymes in eukaryotes. Studies in vitro have provided little evidence of anticipated protein-protein interactions that would enable substrate channeling and regulation of the metabolic flux. We applied fluorescence microscopy to HeLa cells and discovered that all six enzymes colocalize to form clusters in the cellular cytoplasm. The association and dissociation of these enzyme clusters can be regulated dynamically, by either changing the purine levels of or adding exogenous agents to the culture media. Collectively, the data provide strong evidence for the formation of a multi-enzyme complex, the "purinosome, " to carry out de novo purine biosynthesis in cells.

Original languageEnglish (US)
Pages (from-to)103-106
Number of pages4
JournalScience
Volume320
Issue number5872
DOIs
StatePublished - Apr 5 2008

All Science Journal Classification (ASJC) codes

  • General

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