Biological assembly 1&nbspassigned by authors and generated by PQS (software)
1O6F
PROLYL OLIGOPEPTIDASE FROM PORCINE BRAIN, D641A MUTANT WITH BOUND PEPTIDE LIGAND SUC-GLY-PRO
DOI: 10.2210/pdb1O6F/pdb
Organism(s): Sus scrofa
Mutation(s): 1
Deposition Author(s): Rea, D., Fulop, V.
Substrate-dependent competency of the catalytic triad of prolyl oligopeptidase.
Szeltner, Z., Rea, D., Juhasz, T., Renner, V., Mucsi, Z., Orosz, G., Fulop, V., Polgar, L.
(2002) J. Biol. Chem. 277: 44597-44605
DOI: 10.1074/jbc.M207386200
1O6G
Also Cited By: 1UOP, 1UOO, 1VZ3, 1VZ2, 1UOQ
Prolyl oligopeptidase, a serine peptidase unrelated to trypsin and subtilisin, is implicated in memory disorders and is an important target of drug design. The catalytic competence of the Asp(641) residue of the catalytic triad (Ser(554), Asp(641), H ...
Prolyl oligopeptidase, a serine peptidase unrelated to trypsin and subtilisin, is implicated in memory disorders and is an important target of drug design. The catalytic competence of the Asp(641) residue of the catalytic triad (Ser(554), Asp(641), His(680)) was studied using the D641N and D641A variants of the enzyme. Both variants displayed 3 orders of magnitude reduction in k(cat)/K(m) for benzyloxycarbonyl-Gly-Pro-2-naphthylamide. Using an octapeptide substrate, the decrease was 6 orders of magnitude, whereas with Z-Gly-Pro-4-nitrophenyl ester there was virtually no change in k(cat)/K(m). This indicates that the contribution of Asp(641) is very much dependent on the substrate-leaving group, which was not the case for the classic serine peptidase, trypsin. The rate constant for benzyloxycarbonyl-Gly-Pro-thiobenzylester conformed to this series as demonstrated by a method designed for monitoring the hydrolysis of thiolesters in the presence of thiol groups. Alkylation of His(680) with Z-Gly-Pro-CH(2)Cl was concluded with similar rate constants for wild-type and D641A variant. However, kinetic measurements with Z-Gly-Pro-OH, a product-like inhibitor, indicated that the His(680) is not accessible in the enzyme variants. Crystal structure determination of these mutants revealed subtle perturbations related to the catalytic activity. Many of these observations show differences in the catalysis between trypsin and prolyl oligopeptidase.
Catalysis of Serine Oligopeptidases is Controlled by a Gating Filter Mechanism
Fulop, V.,Szeltner, Z.,Polgar, L.
(2000) Embo Rep. 1: 277
Structures of Prolyl Oligopeptidase Substrate/ Inhibitor Complexes. Use of Inhibitor Bindtitration of the Catalytic Histidine Residueing for
Fulop, V.,Szeltner, Z.,Renner, V.,Polgar, L.
(2001) J.Biol.Chem. 276: 1262
Prolyl Oligopeptidase: An Unusual Beta-Propeller Domain Regulates Proteolysis
Fulop, V.,Bocskei, Z.,Polgar, L.
(1998) Cell 94: 161
Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, H-1518, P. O. Box 7, Budapest 112, Hungary.
Prolyl endopeptidase
710 Sus scrofa Mutation(s): 1
Gene Names: PREP
EC: 3.4.21.26
Find proteins for P23687 (Sus scrofa)
Go to Gene View: PREP
GLY
Query on GLY
DHMQDGOQFOQNFH-UHFFFAOYSA-N
Query on SIN
SUCCINIC ACID
KDYFGRWQOYBRFD-UHFFFAOYSA-N
Query on PRO
ONIBWKKTOPOVIA-BYPYZUCNSA-N
a = 71.400 α = 90.00
SCALEPACK data scaling
CCP4 phasing
DENZO data reduction
X-PLOR phasing
X-PLOR refinement
Type: Advisory, Data collection, Derived calculations
Type: Data collection, Database references, Source and taxonomy, Structure summary