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PDBsum entry 1e5t
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Hydrolase PDB id
1e5t

 

 

 

 

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Contents
Protein chain
710 a.a. *
Ligands
GOL ×9
Waters ×866
* Residue conservation analysis
PDB id:
1e5t
Name: Hydrolase
Title: Prolyl oligopeptidase from porcine brain, mutant
Structure: Prolyl endopeptidase. Chain: a. Synonym: prolyl endopeptidase, post-proline cleaving enzyme, pe. Engineered: yes. Mutation: yes
Source: Sus scrofa. Pig. Organism_taxid: 9823. Tissue: brain. Cellular_location: cytoplasm. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.70Å     R-factor:   0.184     R-free:   0.206
Authors: V.Fulop
Key ref:
V.Fülöp et al. (2000). Catalysis of serine oligopeptidases is controlled by a gating filter mechanism. Embo Rep, 1, 277-281. PubMed id: 11256612 DOI: 10.1093/embo-reports/kvd048
Date:
02-Aug-00     Release date:   01-Oct-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P23687  (PPCE_PIG) -  Prolyl endopeptidase from Sus scrofa
Seq:
Struc: 		 
Seq:
Struc: 		710 a.a.
710 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.4.21.26  - prolyl oligopeptidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of Pro-|-Xaa >> Ala-|-Xaa in oligopeptides.

 

 
DOI no: 10.1093/embo-reports/kvd048 Embo Rep 1:277-281 (2000)
PubMed id: 11256612  
 
 
Catalysis of serine oligopeptidases is controlled by a gating filter mechanism.
V.Fülöp, Z.Szeltner, L.Polgár.
 
  ABSTRACT  
 
Proteases have a variety of strategies for selecting substrates in order to prevent uncontrolled protein degradation. A recent crystal structure determination of prolyl oligopeptidase has suggested a way for substrate selection involving an unclosed seven-bladed beta-propeller domain. We have engineered a disulfide bond between the first and seventh blades of the propeller, which resulted in the loss of enzymatic activity. These results provided direct evidence for a novel strategy of regulation in which oscillating propeller blades act as a gating filter during catalysis, letting small peptide substrates into the active site while excluding large proteins to prevent accidental proteolysis.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 Oxidation of prolyl oligopeptidase variants. Reaction of the enzymes was carried out with 1.0 mM oxidized glutathione at pH 9.0 and 28°C. Open circles, C78A/C255T variant; filled circles, C255T/Q397C variant. The curves represent single exponential decays. 		Figure 2.
Figure 2 Electron density around the disulfide bond of the C255T/Q397C variant of prolyl oligopeptidase. The SIGMAA (Read, 1986) weighted 2mF[o] - DF[c] electron density using phases from the final model is contoured at 1 level, where represents the r.m.s. electron density for the unit cell. Contours >1.4 Å from any of the displayed atoms have been removed for clarity. The position of the Glu397 side chain of the wild-type enzyme is also shown in thin lines. The picture was drawn with MolScript (Kraulis, 1991; Esnouf, 1997).
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: Embo Rep (2000, 1, 277-281) copyright 2000.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20370893 J.Tenorio-Laranga, F.Coret-Ferrer, B.Casanova-Estruch, M.Burgal, and J.A.García-Horsman (2010).
Prolyl oligopeptidase is inhibited in relapsing-remitting multiple sclerosis.
  J Neuroinflammation, 7, 23.  
19820087 N.C.Ammerman, J.J.Gillespie, A.F.Neuwald, B.W.Sobral, and A.F.Azad (2009).
A typhus group-specific protease defies reductive evolution in rickettsiae.
  J Bacteriol, 191, 7609-7613.  
18820015 Y.Nakajima, K.Ito, T.Toshima, T.Egawa, H.Zheng, H.Oyama, Y.F.Wu, E.Takahashi, K.Kyono, and T.Yoshimoto (2008).
Dipeptidyl aminopeptidase IV from Stenotrophomonas maltophilia exhibits activity against a substrate containing a 4-hydroxyproline residue.
  J Bacteriol, 190, 7819-7829.
PDB code: 2ecf
16385448 J.Jaeken, K.Martens, I.Francois, F.Eyskens, C.Lecointre, R.Derua, S.Meulemans, J.W.Slootstra, E.Waelkens, F.de Zegher, J.W.Creemers, and G.Matthijs (2006).
Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome.
  Am J Hum Genet, 78, 38-51.  
16913837 K.Martens, R.Derua, S.Meulemans, E.Waelkens, J.Jaeken, G.Matthijs, and J.W.Creemers (2006).
PREPL: a putative novel oligopeptidase propelled into the limelight.
  Biol Chem, 387, 879-883.  
15738423 L.Shan, I.I.Mathews, and C.Khosla (2005).
Structural and mechanistic analysis of two prolyl endopeptidases: role of interdomain dynamics in catalysis and specificity.
  Proc Natl Acad Sci U S A, 102, 3599-3604.
PDB codes: 1yr2 2bkl
15678420 M.Groll, M.Bochtler, H.Brandstetter, T.Clausen, and R.Huber (2005).
Molecular machines for protein degradation.
  Chembiochem, 6, 222-256.  
16195597 N.T.Diderot, N.Silvere, A.Yasin, S.Zareen, Z.Fabien, T.Etienne, M.I.Choudhary, and Atta-Ur-Rahman (2005).
Prolyl endopeptidase and thrombin inhibitory diterpenoids from the bark of Xylopia aethiopica.
  Biosci Biotechnol Biochem, 69, 1763-1766.  
15644339 R.E.Morty, R.Pellé, I.Vadász, G.L.Uzcanga, W.Seeger, and J.Bubis (2005).
Oligopeptidase B from Trypanosoma evansi. A parasite peptidase that inactivates atrial natriuretic factor in the bloodstream of infected hosts.
  J Biol Chem, 280, 10925-10937.  
15950352 R.S.Williams (2005).
Pharmacogenetics in model systems: defining a common mechanism of action for mood stabilisers.
  Prog Neuropsychopharmacol Biol Psychiatry, 29, 1029-1037.  
14986307 G.Bellemère, H.Vaudry, L.Mounien, I.Boutelet, and S.Jégou (2004).
Localization of the mRNA encoding prolyl endopeptidase in the rat brain and pituitary.
  J Comp Neurol, 471, 128-143.  
15175333 J.R.Bjelke, J.Christensen, S.Branner, N.Wagtmann, C.Olsen, A.B.Kanstrup, and H.B.Rasmussen (2004).
Tyrosine 547 constitutes an essential part of the catalytic mechanism of dipeptidyl peptidase IV.
  J Biol Chem, 279, 34691-34697.
PDB codes: 1tk3 1tkr 1to7 1u8e
14718659 K.Aertgeerts, S.Ye, M.G.Tennant, M.L.Kraus, J.Rogers, B.C.Sang, R.J.Skene, D.R.Webb, and G.S.Prasad (2004).
Crystal structure of human dipeptidyl peptidase IV in complex with a decapeptide reveals details on substrate specificity and tetrahedral intermediate formation.
  Protein Sci, 13, 412-421.
PDB codes: 1r9m 1r9n
12655644 B.Eisenhaber, S.Maurer-Stroh, M.Novatchkova, G.Schneider, and F.Eisenhaber (2003).
Enzymes and auxiliary factors for GPI lipid anchor biosynthesis and post-translational transfer to proteins.
  Bioessays, 25, 367-385.  
12832764 C.Oefner, A.D'Arcy, A.Mac Sweeney, S.Pierau, R.Gardiner, and G.E.Dale (2003).
High-resolution structure of human apo dipeptidyl peptidase IV/CD26 and its complex with 1-[([2-[(5-iodopyridin-2-yl)amino]-ethyl]amino)-acetyl]-2-cyano-(S)-pyrrolidine.
  Acta Crystallogr D Biol Crystallogr, 59, 1206-1212.
PDB code: 1pfq
14517548 G.Meng, and K.Fütterer (2003).
Structural framework of fructosyl transfer in Bacillus subtilis levansucrase.
  Nat Struct Biol, 10, 935-941.
PDB codes: 1oyg 1pt2
12483204 H.B.Rasmussen, S.Branner, F.C.Wiberg, and N.Wagtmann (2003).
Crystal structure of human dipeptidyl peptidase IV/CD26 in complex with a substrate analog.
  Nat Struct Biol, 10, 19-25.
PDB code: 1n1m
12906826 R.Thoma, B.Löffler, M.Stihle, W.Huber, A.Ruf, and M.Hennig (2003).
Structural basis of proline-specific exopeptidase activity as observed in human dipeptidyl peptidase-IV.
  Structure, 11, 947-959.
PDB codes: 1nu6 1nu8
14514675 Z.Szeltner, D.Rea, V.Renner, L.Juliano, V.Fülop, and L.Polgár (2003).
Electrostatic environment at the active site of prolyl oligopeptidase is highly influential during substrate binding.
  J Biol Chem, 278, 48786-48793.
PDB codes: 1uoo 1uop 1uoq
12437101 H.Brandstetter, J.S.Kim, M.Groll, P.Göttig, and R.Huber (2002).
Structural basis for the processive protein degradation by tricorn protease.
  Biol Chem, 383, 1157-1165.  
12029050 R.E.Morty, V.Fülöp, and N.W.Andrews (2002).
Substrate recognition properties of oligopeptidase B from Salmonella enterica serovar Typhimurium.
  J Bacteriol, 184, 3329-3337.  
11900553 T.Juhász, Z.Szeltner, V.Renner, and L.Polgár (2002).
Role of the oxyanion binding site and subsites S1 and S2 in the catalysis of oligopeptidase B, a novel target for antimicrobial chemotherapy.
  Biochemistry, 41, 4096-4106.  
12228249 Z.Szeltner, D.Rea, T.Juhász, V.Renner, Z.Mucsi, G.Orosz, V.Fülöp, and L.Polgár (2002).
Substrate-dependent competency of the catalytic triad of prolyl oligopeptidase.
  J Biol Chem, 277, 44597-44605.
PDB codes: 1o6f 1o6g
12202494 Z.Szeltner, D.Rea, V.Renner, V.Fulop, and L.Polgar (2002).
Electrostatic effects and binding determinants in the catalysis of prolyl oligopeptidase. Site specific mutagenesis at the oxyanion binding site.
  J Biol Chem, 277, 42613-42622.
PDB codes: 1h2w 1h2x 1h2y 1h2z
11719810 H.Brandstetter, J.S.Kim, M.Groll, and R.Huber (2001).
Crystal structure of the tricorn protease reveals a protein disassembly line.
  Nature, 414, 466-470.
PDB code: 1k32
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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