Biological Activities of Lasso Peptides and Structure–Activity Relationships - Lasso Peptides: Bacterial Strategies to Make and Maintain Bioactive Entangled Scaffolds - page 48

a

1 10

D R V Y I H P F H L

Angiotensin I

1 9

Arginine-vasopressin

C Y F Q N C P R G

1 9

R P P G F S P F R

Bradykinin

1 10

Gonadotropin releasing hormone (GnRH)

pE H W S Y G L R P G NH 2

1 13

Neurotensin

pE L Y E N K P R R P Y I L

1 9

Oxytocin

C Y I Q N C P L G

NH 2

1 11

Substance P R P K P Q Q F F G L M

1 3

Thyrotropin-releasing hormone (TRH)

pE H P NH 2

b

Z-Pro-Prolinal JTP-4819 ONO-1603 UAMC-00021

SUAM-1221 S 17092 Y-29794

c

Propep n

1

Y

P

G

18

9

W

D L F G G H T F I S P

W

R

D

Y

Fig. 3.5 Prolyloligopeptidase and main substrates and inhibitors. a Selected substrates of proly-
loligopeptidase (Garcia-Horsman et al. 2007 ; Lawandi et al. 2010 ). pE: pyroglutamate. b Main
inhibitors of prolyloligopeptidase: Z-Pro-Prolinal, JTP-4819, ONO-1603, SUAM-1221, S 17092,
Y-29794, UAMC-00021 (Garcia-Horsman et al. 2007 ; Lawandi et al. 2010 ). c Primary structure
of propeptin

prolyloligopeptidase activity has been observed in patients suffering from different
stages of depression, while an increased activity has been detected for patients with
mania and schizophrenia (Maes et al. 1994 , 1995 ). The activity of prolyloligopep-
tidase in relation with mood stabilization, learning and memory has been related to
the control of inositol, which is an important cellular second messenger (Williams
et al. 1999 , 2005 ; Schulz et al. 2002 ).
The three-dimensional structure of prolyloligopeptidase (Fulop et al. 1998 )
solved for the porcine homologue, which is more than 97 % identical in sequence
to the human protein (Lawandi et al. 2010 ), shows a two-domain structure, with a