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PDBsum entry 2iwa

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protein ligands metals links
Transferase PDB id
2iwa
Jmol
Contents
Protein chain
254 a.a. *
Ligands
NAG ×2
GOL ×5
Metals
_CA
Waters ×309
* Residue conservation analysis
PDB id:
2iwa
Name: Transferase
Title: Unbound glutaminyl cyclotransferase from carica papaya.
Structure: Glutamine cyclotransferase. Chain: a. Engineered: yes. Other_details: glycosylation at asn53 and asn123
Source: Carica papaya. Papaya. Organism_taxid: 3649. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: highfive.
Resolution:
1.60Å     R-factor:   0.148     R-free:   0.168
Authors: T.Guevara,N.Mallorqui-Fernandez,R.Garcia-Castellanos,G.E.Pet C.Lauritzen,J.Pedersen,J.Arnau,F.X.Gomis-Ruth,M.Sola
Key ref: T.Guevara et al. (2006). Papaya glutamine cyclotransferase shows a singular five-fold beta-propeller architecture that suggests a novel reaction mechanism. Biol Chem, 387, 1479-1486. PubMed id: 17081122
Date:
27-Jun-06     Release date:   04-Jul-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O81226  (O81226_CARPA) -  Glutamine cyclotransferase
Seq:
Struc:
288 a.a.
254 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.3.2.5  - Glutaminyl-peptide cyclotransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-glutaminyl-peptide = 5-oxoprolyl-peptide + NH3
L-glutaminyl-peptide
= 5-oxoprolyl-peptide
+ NH(3)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   1 term 
  Biochemical function     transferase activity     4 terms  

 

 
    Added reference    
 
 
Biol Chem 387:1479-1486 (2006)
PubMed id: 17081122  
 
 
Papaya glutamine cyclotransferase shows a singular five-fold beta-propeller architecture that suggests a novel reaction mechanism.
T.Guevara, N.Mallorquí-Fernández, R.García-Castellanos, S.García-Piqué, G.Ebert Petersen, C.Lauritzen, J.Pedersen, J.Arnau, F.X.Gomis-Rüth, M.Solà.
 
  ABSTRACT  
 
Cyclisation of N-terminal glutamine and/or glutamate to yield pyroglutamate is an essential posttranslational event affecting a plethora of bioactive peptides and proteins. It is directly linked with pathologies ranging from neurodegenerative diseases to inflammation and several types of cancers. The reaction is catalysed by ubiquitous glutaminyl cyclotransferases (QCs), which present two distinct prototypes. Mammalian QCs are zinc-dependent enzymes with an alpha/beta-hydrolase fold. Here we present the 1.6-A-resolution structure of the other prototype, the plant analogue from Carica papaya (PQC). The hatbox-shaped molecule consists of an unusual five-fold beta-propeller traversed by a central channel, a topology that has hitherto been described only for some sugar-binding proteins and an extracellular nucleotidase. The high resistance of the enzyme to denaturation and proteolytic degradation is explained by its architecture, which is uniquely stabilised by a series of tethering elements that confer rigidity. Strikingly, the N-terminus of PQC specifically interacts with residues around the entrance to the central channel of a symmetry-related molecule, suggesting that this location is the putative active site. Cyclisation would follow a novel general-acid/base working mechanism, pivoting around a strictly conserved glutamate. This study provides a lead structure not only for plant QC orthologues, but also for bacteria, including potential human pathogens causing diphtheria, plague and malaria.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20868223 D.R.Carrillo, C.Parthier, N.Jänckel, J.Grandke, M.Stelter, S.Schilling, M.Boehme, P.Neumann, R.Wolf, H.U.Demuth, M.T.Stubbs, and J.U.Rahfeld (2010).
Kinetic and structural characterization of bacterial glutaminyl cyclases from Zymomonas mobilis and Myxococcus xanthus.
  Biol Chem, 391, 1419-1428.
PDB codes: 3nok 3nol 3nom
18470930 M.Calvaresi, M.Garavelli, and A.Bottoni (2008).
Computational evidence for the catalytic mechanism of glutaminyl cyclase. A DFT investigation.
  Proteins, 73, 527-538.  
18979624 S.Schilling, C.Wasternack, and H.U.Demuth (2008).
Glutaminyl cyclases from animals and plants: a case of functionally convergent protein evolution.
  Biol Chem, 389, 983-991.  
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