PDBsum entry 1vz3

Hydrolase

PDB id: 1vz3

Contents

Protein chain

710 a.a. *

Ligands

GOL ×5

Waters ×1161

* Residue conservation analysis

PDB id:

1vz3

Name:

Hydrolase

Title:

Prolyl oligopeptidase from porcine brain, t597c mutant

Structure:

Prolyl endopeptidase. Chain: a. Synonym: post-proline cleaving enzyme, pe, prep. Engineered: yes. Mutation: yes. Other_details: engineered mutation thr 597 cys

Source:

Sus scrofa. Pig. Organism_taxid: 9823. Tissue: brain. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.60Å R-factor: 0.162 R-free: 0.193

Authors:

D.Rea,V.Fulop

Key ref:

Z.Szeltner et al. (2004). Concerted structural changes in the peptidase and the propeller domains of prolyl oligopeptidase are required for substrate binding. J Mol Biol, 340, 627-637. PubMed id: 15210359 DOI: 10.1016/j.jmb.2004.05.011

Date:

14-May-04 Release date: 01-Jul-04

Protein chain

P23687  (PPCE_PIG) -  Prolyl endopeptidase from Sus scrofa

Seq: 710 a.a.

Struc: 710 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.4.21.26 - prolyl oligopeptidase.
• Reaction: Hydrolysis of Pro-|-Xaa >> Ala-|-Xaa in oligopeptides.

DOI no: 10.1016/j.jmb.2004.05.011

J Mol Biol 340:627-637 (2004)

PubMed id: 15210359

Concerted structural changes in the peptidase and the propeller domains of prolyl oligopeptidase are required for substrate binding.

Z.Szeltner, D.Rea, T.Juhász, V.Renner, V.Fülöp, L.Polgár.

ABSTRACT

Prolyl oligopeptidase contains a peptidase domain and its catalytic triad is covered by the central tunnel of a seven-bladed beta-propeller. This domain makes the enzyme an oligopeptidase by excluding large structured peptides from the active site. The apparently rigid crystal structure does not explain how the substrate can approach the catalytic groups. Two possibilities of substrate access were investigated: either blades 1 and 7 of the propeller domain move apart, or the peptidase and/or propeller domains move to create an entry site at the domain interface. Engineering disulfide bridges to the expected oscillating structures prevented such movements, which destroyed the catalytic activity and precluded substrate binding. This indicated that concerted movements of the propeller and the peptidase domains are essential for the enzyme action.

Selected figure(s)

Figure 4.
Figure 4. Oxidation of prolyl oligopeptidase variants by air. The activity of the T597C variant was measured with Z-Gly-Pro-Nap (0m) or Abz-Gly-Phe-Gly-Pro-Phe-Gly-Phe(NO[2])-Ala-NH[2] (+). The C255A variant was used as control ( triangle, open ).

Figure 5.
Figure 5. Reactivation of the oxidized T597C variant of prolyl oligopeptidase. Reduction of the disulfide bond was achieved with 1.5 mM DTE.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 340, 627-637) copyright 2004.

Figures were selected by an automated process.