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PDBsum entry 1iyd

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protein ligands Protein-protein interface(s) links
Transferase PDB id
1iyd
Jmol
Contents
Protein chains
304 a.a. *
Ligands
PLP ×3
GUA ×3
Waters ×311
* Residue conservation analysis
PDB id:
1iyd
Name: Transferase
Title: Crystal structure of eschelichia coli branched-chain amino a aminotransferase
Structure: Branched-chain amino acid aminotransferase. Chain: a, b, c. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Hexamer (from PDB file)
Resolution:
2.15Å     R-factor:   0.205     R-free:   0.242
Authors: K.Hirotsu,M.Goto
Key ref:
M.Goto et al. (2003). Crystal structures of branched-chain amino acid aminotransferase complexed with glutamate and glutarate: true reaction intermediate and double substrate recognition of the enzyme. Biochemistry, 42, 3725-3733. PubMed id: 12667063 DOI: 10.1021/bi026722f
Date:
07-Aug-02     Release date:   06-May-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0AB80  (ILVE_ECOLI) -  Branched-chain-amino-acid aminotransferase
Seq:
Struc:
309 a.a.
304 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.6.1.42  - Branched-chain-amino-acid transaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Leucine Biosynthesis
      Reaction:
1. L-leucine + 2-oxoglutarate = 4-methyl-2-oxopentanoate + L-glutamate
2. L-isoleucine + 2-oxoglutarate = (S)-3-methyl-2-oxopentanoate + L-glutamate
3. L-valine + 2-oxoglutarate = 3-methyl-2-oxobutanoate + L-glutamate
L-leucine
+
2-oxoglutarate
Bound ligand (Het Group name = GUA)
matches with 90.00% similarity
= 4-methyl-2-oxopentanoate
+ L-glutamate
L-isoleucine
+ 2-oxoglutarate
= (S)-3-methyl-2-oxopentanoate
+
L-glutamate
Bound ligand (Het Group name = GUA)
matches with 90.00% similarity
L-valine
+ 2-oxoglutarate
= 3-methyl-2-oxobutanoate
+
L-glutamate
Bound ligand (Het Group name = GUA)
matches with 90.00% similarity
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Bound ligand (Het Group name = PLP) matches with 93.75% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   8 terms 
  Biochemical function     catalytic activity     8 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi026722f Biochemistry 42:3725-3733 (2003)
PubMed id: 12667063  
 
 
Crystal structures of branched-chain amino acid aminotransferase complexed with glutamate and glutarate: true reaction intermediate and double substrate recognition of the enzyme.
M.Goto, I.Miyahara, H.Hayashi, H.Kagamiyama, K.Hirotsu.
 
  ABSTRACT  
 
Branched-chain amino acid aminotransferase (BCAT), which has pyridoxal 5'-phosphate as a cofactor, is a key enzyme in the biosynthetic pathway of hydrophobic amino acids (leucine, isoleucine, and valine). The enzyme reversibly catalyzes the transfer of the amino group of a hydrophobic amino acid to 2-oxoglutarate to form a 2-oxo acid and glutamate. Therefore, the active site of BCAT should have a mechanism to enable recognition of an acidic amino acid as well as a hydrophobic amino acid (double substrate recognition). The three-dimensional structures of Escherichia coli BCAT (eBCAT) in complex with the acidic substrate (glutamate) and the acidic substrate analogue (glutarate) have been determined by X-ray diffraction at 1.82 and 2.15 A resolution, respectively. The enzyme is a homo hexamer, with the polypeptide chain of the subunit folded into small and large domains, and an interdomain loop. The eBCAT in complex with the natural substrate, glutamate, was assigned as a ketimine as the most probable form based upon absorption spectra of the crystal complex and the shape of the residual electron density corresponding to the cofactor-glutamate bond structure. Upon binding of an acidic substrate, the interdomain loop approaches the substrate to shield it from the solvent region, as observed in the complex with a hydrophobic substrate. Both the acidic and the hydrophobic side chains of the substrates are bound to almost the same position in the pocket of the enzyme and are identical in structure. The inner side of the pocket is mostly hydrophobic to accommodate the hydrophobic side chain but has four sites to coordinate with the gamma-carboxylate of glutamate. The mechanism for the double substrate recognition observed in eBCAT is in contrast to those in aromatic amino acid and histidinol-phosphate aminotransferases. In an aromatic amino acid aminotransferase, the acidic side chain is located at the same position as that for the aromatic side chain because of large-scale rearrangements of the hydrogen bond network. In the histidinol-phosphate aminotransferase, the acidic and basic side chains are located at different sites and interact with different residues of the disordered loop.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20871599 M.Höhne, S.Schätzle, H.Jochens, K.Robins, and U.T.Bornscheuer (2010).
Rational assignment of key motifs for function guides in silico enzyme identification.
  Nat Chem Biol, 6, 807-813.  
  19923721 L.W.Tremblay, and J.S.Blanchard (2009).
The 1.9 A structure of the branched-chain amino-acid transaminase (IlvE) from Mycobacterium tuberculosis.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 1071-1077.
PDB code: 3ht5
18831049 T.Tomita, T.Miyagawa, T.Miyazaki, S.Fushinobu, T.Kuzuyama, and M.Nishiyama (2009).
Mechanism for multiple-substrates recognition of alpha-aminoadipate aminotransferase from Thermus thermophilus.
  Proteins, 75, 348-359.
PDB codes: 2zp7 3cbf
18560156 J.Marienhagen, T.Sandalova, H.Sahm, L.Eggeling, and G.Schneider (2008).
Insights into the structural basis of substrate recognition by histidinol-phosphate aminotransferase from Corynebacterium glutamicum.
  Acta Crystallogr D Biol Crystallogr, 64, 675-685.
PDB codes: 3cq4 3cq5 3cq6
16699828 J.A.McCourt, and R.G.Duggleby (2006).
Acetohydroxyacid synthase and its role in the biosynthetic pathway for branched-chain amino acids.
  Amino Acids, 31, 173-210.  
17050531 N.H.Yennawar, M.M.Islam, M.Conway, R.Wallin, and S.M.Hutson (2006).
Human mitochondrial branched chain aminotransferase isozyme: structural role of the CXXC center in catalysis.
  J Biol Chem, 281, 39660-39671.
PDB codes: 2hdk 2hg8 2hgw 2hgx 2hhf
15889412 K.Hirotsu, M.Goto, A.Okamoto, and I.Miyahara (2005).
Dual substrate recognition of aminotransferases.
  Chem Rec, 5, 160-172.  
16141215 M.Goto, I.Miyahara, K.Hirotsu, M.Conway, N.Yennawar, M.M.Islam, and S.M.Hutson (2005).
Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin.
  J Biol Chem, 280, 37246-37256.
PDB codes: 2a1h 2cog 2coi 2coj
15189147 A.C.Eliot, and J.F.Kirsch (2004).
Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations.
  Annu Rev Biochem, 73, 383-415.  
14761974 M.Goto, R.Omi, I.Miyahara, A.Hosono, H.Mizuguchi, H.Hayashi, H.Kagamiyama, and K.Hirotsu (2004).
Crystal structures of glutamine:phenylpyruvate aminotransferase from Thermus thermophilus HB8: induced fit and substrate recognition.
  J Biol Chem, 279, 16518-16525.
PDB codes: 1v2d 1v2e 1v2f
12952961 R.Omi, M.Goto, I.Miyahara, H.Mizuguchi, H.Hayashi, H.Kagamiyama, and K.Hirotsu (2003).
Crystal structures of threonine synthase from Thermus thermophilus HB8: conformational change, substrate recognition, and mechanism.
  J Biol Chem, 278, 46035-46045.
PDB codes: 1uim 1uin 1uiq 1v7c
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.