Glycine 384 is required for presenilin-1 function and is conserved in bacterial polytopic aspartyl proteases

Endoproteolysis of beta -amyloid precursor protein (beta APP) and Notch req uires conserved aspartate residues in presenilins 1 and 2 (PS1 and PS2). Al though PS1 and PS2 have therefore been proposed to be aspartyl proteases, n o homology to other aspartyl proteases has been found. Here we identify hom ology between the presenilin active site and polytopic aspartyl proteases o f bacterial origin, thus supporting the hypothesis that presenilins are nov el aspartyl proteases.