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  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 .