Glycine 384 is required for presenilin-1 function and is conserved in bacterial polytopic aspartyl proteases.
Endoproteolysis of beta-amyloid precursor protein (betaAPP) and Notch requires conserved aspartate residues in presenilins 1 and 2 (PS1 and PS2). Although PS1 and PS2 have therefore been proposed to be aspartyl proteases, no homology to other aspartyl proteases has been found. Here we identify homology between the presenilin active site and polytopic aspartyl proteases of bacterial origin, thus supporting the hypothesis that presenilins are novel aspartyl proteases.
Steiner
H
H
Adolf Butenandt-Institute, Department of Biochemistry, Laboratory for Alzheimer's Disease Research, Ludwig-Maximilians-University, 80336 Munich, Germany.
Kostka
M
M
Romig
H
H
Basset
G
G
Pesold
B
B
Hardy
J
J
Capell
A
A
Meyn
L
L
Grim
M L
ML
Baumeister
R
R
Fechteler
K
K
Haass
C
C
D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D001419:Bacteria / Q000201:enzymology; D001426:Bacterial Proteins / Q000378:metabolism; D002460:Cell Line; D017124:Conserved Sequence; D010450:Endopeptidases; D005998:Glycine / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000378:metabolism; D053764:Presenilin-1; D053766:Presenilin-2; D051880:Receptors, Notch
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001426:Bacterial Proteins; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D053766:Presenilin-2; D051880:Receptors, Notch; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D010450:Endopeptidases; C067127:prepilin peptidase protein, Bacteria; D016282:Aspartic Acid Endopeptidases; D005998:Glycine