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PDBsum entry 1ay5
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protein ligands Protein-protein interface(s) links
Transferase PDB id
1ay5

 

 

 

 

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Contents
Protein chains
394 a.a. *
Ligands
PLP ×2
MAE ×2
Waters ×248
* Residue conservation analysis
PDB id:
1ay5
Name: Transferase
Title: Aromatic amino acid aminotransferase complex with maleate
Structure: Aromatic amino acid aminotransferase. Chain: a, b. Synonym: aroat. Engineered: yes
Source: Paracoccus denitrificans. Organism_taxid: 266. Strain: ifo12442. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.50Å     R-factor:   0.171     R-free:   0.245
Authors: A.Okamoto,K.Hirotsu,H.Kagamiyama
Key ref:
A.Okamoto et al. (1998). Crystal structures of Paracoccus denitrificans aromatic amino acid aminotransferase: a substrate recognition site constructed by rearrangement of hydrogen bond network. J Mol Biol, 280, 443-461. PubMed id: 9665848 DOI: 10.1006/jmbi.1998.1869
Date:
14-Nov-97     Release date:   14-Oct-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P95468  (TYRB_PARDE) -  Aromatic-amino-acid aminotransferase from Paracoccus denitrificans
Seq:
Struc: 		394 a.a.
394 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.6.1.57  - aromatic-amino-acid transaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Phenylalanine and Tyrosine Biosynthesis
      Reaction: an aromatic L-alpha-amino acid + 2-oxoglutarate = an aromatic oxo-acid + L-glutamate
aromatic L-alpha-amino acid
Bound ligand (Het Group name = MAE)
matches with 63.64% similarity 		+ 2-oxoglutarate
 = aromatic oxo-acid
 + L-glutamate
      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

 

 
    reference    
 
 
DOI no: 10.1006/jmbi.1998.1869 J Mol Biol 280:443-461 (1998)
PubMed id: 9665848  
 
 
Crystal structures of Paracoccus denitrificans aromatic amino acid aminotransferase: a substrate recognition site constructed by rearrangement of hydrogen bond network.
A.Okamoto, Y.Nakai, H.Hayashi, K.Hirotsu, H.Kagamiyama.
 
  ABSTRACT  
 
Aminotransferase reversibly catalyzes the transamination reaction by a ping-pong bi-bi mechanism with pyridoxal 5'-phosphate (PLP) as a cofactor. Various kinds of aminotransferases developing into catalysts for particular substrates have been reported. Among the aminotransferases, aromatic amino acid aminotransferase (EC 2.6.1. 57) catalyzes the transamination reaction with both acidic substrates and aromatic substrates. To elucidate the multiple substrate recognition mechanism, we determined the crystal structures of aromatic amino acid aminotransferase from Paracoccus denitrificans (pdAroAT): unliganded pdAroAT, pdAroAT in a complex with maleate as an acidic substrate analog, and pdAroAT in a complex with 3-phenylpropionate as an aromatic substrate analog at 2.33 A, 2. 50 A and 2.30 A resolution, respectively. The pdAroAT molecule is a homo-dimer. Each subunit has 394 amino acids and one PLP and is divided into small and large domains. The overall structure of pdAroAT is essentially identical to that of aspartate aminotransferase (AspAT) which catalyzes the transamination reaction with only an acidic amino acid. On binding the acidic substrate analog, arginine 292 and 386 form end-on salt bridges with carboxylates of the analog. Furthermore, binding of the substrate induces the domain movement to close the active site. The recognition mechanism for the acidic substrate analog in pdAroAT is identical to that observed in AspAT. Binding of the aromatic substrate analog causes reorientation of the side-chain of the residues, lysine 16, asparagine 142, arginine 292* and serine 296*, and changes in the position of water molecules in the active site to form a new hydrogen bond network in contrast to the active site structure of pdAroAT in the complex with an acidic substrate analog. Consequently, the rearrangement of the hydrogen bond network can form recognition sites for both acidic and aromatic side-chains of the substrate without a conformational change in the backbone structure in pdAroAT.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Ribbon drawing of a molecule of unliganded pdAroAT viewed along the molecular dyad. α-Helices are colored red and β-strands yellow. PLP is indicated by the ball-and-stick model. Only in subunit A, the α-helices are numbered and N and C-terminals are indicated by N and C, respectively. Figure produced with MOLSCRIPT [Kraulis 1991]. 		Figure 2.
Figure 2. Active site structures. PLP and inhibitor are indicated by open bonds and water molecules by the filled circles. (a) The active site in subunit B of the unliganded pdAroAT; (b) the active site in subunit B of the maleate complex of pdAroAT and (c) the active site in subunit B of the 3-phenylpropionate complex of pdAroAT. Produced with the program ORTEP-II [Johnson 1976].
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1998, 280, 443-461) copyright 1998.  
  Figures were selected by an automated process.  

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.  
19826765 Q.Han, T.Cai, D.A.Tagle, and J.Li (2010).
Structure, expression, and function of kynurenine aminotransferases in human and rodent brains.
  Cell Mol Life Sci, 67, 353-368.
PDB code: 3hlm
19338303 Q.Han, H.Robinson, T.Cai, D.A.Tagle, and J.Li (2009).
Structural insight into the inhibition of human kynurenine aminotransferase I/glutamine transaminase K.
  J Med Chem, 52, 2786-2793.
PDB codes: 3fvs 3fvu 3fvx
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
18931110 N.J.Zelyas, H.Cai, T.Kwong, and S.E.Jensen (2008).
Alanylclavam biosynthetic genes are clustered together with one group of clavulanic acid biosynthetic genes in Streptomyces clavuligerus.
  J Bacteriol, 190, 7957-7965.  
18186649 Q.Han, Y.G.Gao, H.Robinson, and J.Li (2008).
Structural insight into the mechanism of substrate specificity of aedes kynurenine aminotransferase.
  Biochemistry, 47, 1622-1630.
PDB codes: 2r5c 2r5e
17683331 I.Matsui, and K.Harata (2007).
Implication for buried polar contacts and ion pairs in hyperthermostable enzymes.
  FEBS J, 274, 4012-4022.  
17259358 J.Kim, D.Kyung, H.Yun, B.K.Cho, J.H.Seo, M.Cha, and B.G.Kim (2007).
Cloning and characterization of a novel beta-transaminase from Mesorhizobium sp. strain LUK: a new biocatalyst for the synthesis of enantiomerically pure beta-amino acids.
  Appl Environ Microbiol, 73, 1772-1782.  
16673402 B.K.Cho, J.H.Seo, T.J.Kang, J.Kim, H.Y.Park, B.S.Lee, and B.G.Kim (2006).
Engineering aromatic L-amino acid transaminase for the asymmetric synthesis of constrained analogs of L-phenylalanine.
  Biotechnol Bioeng, 94, 842-850.  
16990263 Q.Han, H.Robinson, Y.G.Gao, N.Vogelaar, S.R.Wilson, M.Rizzi, and J.Li (2006).
Crystal structures of Aedes aegypti alanine glyoxylate aminotransferase.
  J Biol Chem, 281, 37175-37182.
PDB codes: 2huf 2hui 2huu
15889412 K.Hirotsu, M.Goto, A.Okamoto, and I.Miyahara (2005).
Dual substrate recognition of aminotransferases.
  Chem Rec, 5, 160-172.  
15189147 A.C.Eliot, and J.F.Kirsch (2004).
Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations.
  Annu Rev Biochem, 73, 383-415.  
15498941 A.Paiardini, F.Bossa, and S.Pascarella (2004).
Evolutionarily conserved regions and hydrophobic contacts at the superfamily level: The case of the fold-type I, pyridoxal-5'-phosphate-dependent enzymes.
  Protein Sci, 13, 2992-3005.  
15210695 B.Cellini, M.Bertoldi, A.Paiardini, S.D'Aguanno, and C.B.Voltattorni (2004).
Site-directed mutagenesis provides insight into racemization and transamination of alanine catalyzed by Treponema denticola cystalysin.
  J Biol Chem, 279, 36898-36905.  
15459908 B.K.Cho, H.Y.Park, J.H.Seo, K.Kinnera, B.S.Lee, and B.G.Kim (2004).
Enzymatic resolution for the preparation of enantiomerically enriched D-beta-heterocyclic alanine derivatives using Escherichia coli aromatic L-amino acid transaminase.
  Biotechnol Bioeng, 88, 512-519.  
14767072 S.C.Rothman, M.Voorhies, and J.F.Kirsch (2004).
Directed evolution relieves product inhibition and confers in vivo function to a rationally designed tyrosine aminotransferase.
  Protein Sci, 13, 763-772.  
12768628 B.K.Cho, J.H.Seo, T.W.Kang, and B.G.Kim (2003).
Asymmetric synthesis of L-homophenylalanine by equilibrium-shift using recombinant aromatic L-amino acid transaminase.
  Biotechnol Bioeng, 83, 226-234.  
12717026 V.R.Sobrado, M.Montemartini-Kalisz, H.M.Kalisz, M.C.De La Fuente, H.J.Hecht, and C.Nowicki (2003).
Involvement of conserved asparagine and arginine residues from the N-terminal region in the catalytic mechanism of rat liver and Trypanosoma cruzi tyrosine aminotransferases.
  Protein Sci, 12, 1039-1050.  
12006485 D.H.Fong, and A.M.Berghuis (2002).
Substrate promiscuity of an aminoglycoside antibiotic resistance enzyme via target mimicry.
  EMBO J, 21, 2323-2331.
PDB codes: 1l8t 1l8u 2b0q
11295433 C.Nowicki, G.R.Hunter, M.Montemartini-Kalisz, W.Blankenfeldt, H.Hecht, and H.M.Kalisz (2001).
Recombinant tyrosine aminotransferase from Trypanosoma cruzi: structural characterization and site directed mutagenesis of a broad substrate specificity enzyme.
  Biochim Biophys Acta, 1546, 268-281.  
11933244 K.Soda, T.Yoshimura, and N.Esaki (2001).
Stereospecificity for the hydrogen transfer of pyridoxal enzyme reactions.
  Chem Rec, 1, 373-384.  
10715115 D.Saadat, and D.H.Harrison (2000).
Mirroring perfection: the structure of methylglyoxal synthase complexed with the competitive inhibitor 2-phosphoglycolate.
  Biochemistry, 39, 2950-2960.
PDB code: 1egh
10673430 G.Schneider, H.Käck, and Y.Lindqvist (2000).
The manifold of vitamin B6 dependent enzymes.
  Structure, 8, R1-R6.  
10671523 I.Matsui, E.Matsui, Y.Sakai, H.Kikuchi, Y.Kawarabayasi, H.Ura, S.Kawaguchi, S.Kuramitsu, and K.Harata (2000).
The molecular structure of hyperthermostable aromatic aminotransferase with novel substrate specificity from Pyrococcus horikoshii.
  J Biol Chem, 275, 4871-4879.
PDB code: 1dju
9930977 A.Okamoto, S.Ishii, K.Hirotsu, and H.Kagamiyama (1999).
The active site of Paracoccus denitrificans aromatic amino acid aminotransferase has contrary properties: flexibility and rigidity.
  Biochemistry, 38, 1176-1184.
PDB codes: 2ay1 2ay2 2ay3 2ay4 2ay5 2ay6 2ay7 2ay8 2ay9
10417420 T.P.Ko, S.P.Wu, W.Z.Yang, H.Tsai, and H.S.Yuan (1999).
Crystallization and preliminary crystallographic analysis of the Escherichia coli tyrosine aminotransferase.
  Acta Crystallogr D Biol Crystallogr, 55, 1474-1477.
PDB code: 3tat
  10595543 W.Blankenfeldt, C.Nowicki, M.Montemartini-Kalisz, H.M.Kalisz, and H.J.Hecht (1999).
Crystal structure of Trypanosoma cruzi tyrosine aminotransferase: substrate specificity is influenced by cofactor binding mode.
  Protein Sci, 8, 2406-2417.
PDB code: 1bw0
9914259 J.N.Jansonius (1998).
Structure, evolution and action of vitamin B6-dependent enzymes.
  Curr Opin Struct Biol, 8, 759-769.  
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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