A new side opening on prolyl oligopeptidase revealed by electron microscopy.
Prolyl oligopeptidase (POP) has gained importance as a target for the treatment of neuropsychiatric diseases and cognitive disturbances. Therefore, a variety of strategies are currently used to identify POP inhibitors. Here we performed electron microscopy (EM) studies of human POP. Our data reveal for the first time the presence of a new side opening in POP that was not observed in any of the crystallographic structures described to date. Finally, molecular dynamics, the relevant normal modes that contribute to the fluctuation of the catalytic triad residues and the algorithm CAVERN also support the existence of a new large side opening on POP.
Tarragó
Teresa
T
Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac, 10, E-08028, Barcelona, Spain.
Martín-Benito
Jaime
J
Sabidó
Eduard
E
Claasen
Birgit
B
Madurga
Sergio
S
Gairí
Margarida
M
Valpuesta
José M
JM
Giralt
Ernest
E
D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D003072:Cognition Disorders / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D000085822:Prolyl Oligopeptidases; D017434:Protein Structure, Tertiary; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015842:Serine Proteinase Inhibitors
D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases