Abstract
SAMHD1 is a GTP-activated nonspecific dNTP triphosphohydrolase that depletes dNTP pools in resting CD4+ T cells and macrophages and effectively restricts infection by HIV-1. We have designed a nonsubstrate dUTP analogue with a methylene bridge connecting the α phosphate and 5′ carbon that potently inhibits SAMHD1. Although pppCH2dU shows apparent competitive inhibition, it acts by a surprising allosteric mechanism that destabilizes active enzyme tetramer.
Original language | English (US) |
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Pages (from-to) | 9822-9825 |
Number of pages | 4 |
Journal | Journal of the American Chemical Society |
Volume | 136 |
Issue number | 28 |
DOIs | |
State | Published - Jul 16 2014 |
ASJC Scopus subject areas
- Catalysis
- Chemistry(all)
- Biochemistry
- Colloid and Surface Chemistry