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PDBsum entry 3paa

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protein ligands links
Transferase PDB id
3paa
Jmol
Contents
Protein chain
396 a.a. *
Ligands
PJ7
PMP
GOL ×11
SO4 ×4
Waters ×422
* Residue conservation analysis
PDB id:
3paa
Name: Transferase
Title: Mechanism of inactivation of e. Coli aspartate aminotransfer (s)-4-amino-4,5-dihydro-2-furancarboxylic acid (s-adfa) ph
Structure: Aspartate aminotransferase. Chain: a. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: aspc. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.90Å     R-factor:   0.139     R-free:   0.184
Authors: D.Liu,E.Pozharski,M.Fu,R.B.Silverman,D.Ringe
Key ref: D.Liu et al. (2010). Mechanism of inactivation of Escherichia coli aspartate aminotransferase by (S)-4-amino-4,5-dihydro-2-furancarboxylic acid . Biochemistry, 49, 10507-10515. PubMed id: 21033689 DOI: 10.1021/bi101325z
Date:
19-Oct-10     Release date:   01-Dec-10    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
D3H0F7  (D3H0F7_ECO44) -  Aspartate aminotransferase
Seq:
Struc:
396 a.a.
396 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.6.1.1  - Aspartate transaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate
L-aspartate
+
2-oxoglutarate
Bound ligand (Het Group name = PJ7)
matches with 80.00% similarity
= oxaloacetate
+ L-glutamate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Bound ligand (Het Group name = PMP) matches with 88.24% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     biosynthetic process   2 terms 
  Biochemical function     catalytic activity     6 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi101325z Biochemistry 49:10507-10515 (2010)
PubMed id: 21033689  
 
 
Mechanism of inactivation of Escherichia coli aspartate aminotransferase by (S)-4-amino-4,5-dihydro-2-furancarboxylic acid .
D.Liu, E.Pozharski, M.Fu, R.B.Silverman, D.Ringe.
 
  ABSTRACT  
 
As a potential drug to treat neurological diseases, the mechanism-based inhibitor (S)-4-amino-4,5-dihydro-2-furancarboxylic acid (S-ADFA) has been found to inhibit the γ-aminobutyric acid aminotransferase (GABA-AT) reaction. To circumvent the difficulties in structural studies of a S-ADFA-enzyme complex using GABA-AT, l-aspartate aminotransferase (l-AspAT) from Escherichia coli was used as a model PLP-dependent enzyme. Crystal structures of the E. coli aspartate aminotransferase with S-ADFA bound to the active site were obtained via cocrystallization at pH 7.5 and 8. The complex structures suggest that S-ADFA inhibits the transamination reaction by forming adducts with the catalytic lysine 246 via a covalent bond while producing 1 equiv of pyridoxamine 5'-phosphate (PMP). Based on the structures, formation of the K246-S-ADFA adducts requires a specific initial binding configuration of S-ADFA in the l-AspAT active site, as well as deprotonation of the ε-amino group of lysine 246 after the formation of the quinonoid and/or ketimine intermediate in the overall inactivation reaction.