PDBsum entry 1tpl

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Lyase(carbon-carbon) PDB id
Protein chains
426 a.a. *
SO4 ×4
Waters ×450
* Residue conservation analysis
PDB id:
Name: Lyase(carbon-carbon)
Title: The three-dimensional structure of tyrosine phenol-lyase
Structure: Tyrosine phenol-lyase. Chain: a, b. Engineered: yes
Source: Citrobacter intermedius. Organism_taxid: 66695
Biol. unit: Tetramer (from PQS)
2.30Å     R-factor:   0.162    
Authors: A.Antson,T.Demidkina,Z.Dauter,E.Harutyunyan,K.Wilson
Key ref:
A.A.Antson et al. (1993). Three-dimensional structure of tyrosine phenol-lyase. Biochemistry, 32, 4195-4206. PubMed id: 7916622 DOI: 10.1021/bi00067a006
25-Nov-92     Release date:   31-Oct-93    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P31013  (TPL_CITFR) -  Tyrosine phenol-lyase
456 a.a.
426 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Tyrosine phenol-lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-tyrosine + H2O = phenol + pyruvate + NH3
+ H(2)O
= phenol
+ pyruvate
+ NH(3)
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     cellular amino acid metabolic process   3 terms 
  Biochemical function     catalytic activity     5 terms  


DOI no: 10.1021/bi00067a006 Biochemistry 32:4195-4206 (1993)
PubMed id: 7916622  
Three-dimensional structure of tyrosine phenol-lyase.
A.A.Antson, T.V.Demidkina, P.Gollnick, Z.Dauter, R.L.von Tersch, J.Long, S.N.Berezhnoy, R.S.Phillips, E.H.Harutyunyan, K.S.Wilson.
Tyrosine phenol-lyase (EC from Citrobacter freundii has been cloned and the primary sequence deduced from the DNA sequence. From the BrCN digest of the NaBH4-reduced holoenzyme, five peptides were purified and sequenced. The amino acid sequences of the peptides agreed with the corresponding parts of the tyrosine phenol-lyase sequence obtained from the gene structure. K257 is the pyridoxal 5'-phosphate binding residue. Assisted by the sequence data, the crystal structure of apotyrosine phenol-lyase, a pyridoxal 5'-phosphate-dependent enzyme, has been refined to an R-factor of 16.2% at 2.3-A resolution using synchrotron radiation diffraction data. The tetrameric molecule has 222 symmetry, with one of the axes coincident with the crystallographic 2-fold symmetry axis of the crystal which belongs to the space group P2(1)2(1)2 with a = 76.0 A, b = 138.3 A, and c = 93.5 A. Each subunit comprises 14 alpha-helices and 16 beta-strands, which fold into a small and a large domain. The coenzyme-binding lysine residue is located at the interface between the large and small domains of one subunit and the large domain of a crystallographically related subunit. The fold of the large, pyridoxal 5'-phosphate binding domain and the location of the active site are similar to that found in aminotransferases. Most of the residues which participate in binding of pyridoxal 5'-phosphate in aminotransferases are conserved in the structure of tyrosine phenol-lyase. Two dimers of tyrosine phenol-lyase, each of which has a domain architecture similar to that found in aspartate aminotransferases, are bound together through a hydrophobic cluster in the center of the molecule and intertwined N-terminal arms.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19780833 E.Rha, S.Kim, S.L.Choi, S.P.Hong, M.H.Sung, J.J.Song, and S.G.Lee (2009).
Simultaneous improvement of catalytic activity and thermal stability of tyrosine phenol-lyase by directed evolution.
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19420686 T.Koyanagi, T.Katayama, H.Suzuki, A.Onishi, K.Yokozeki, and H.Kumagai (2009).
Hyperproduction of 3,4-dihydroxyphenyl-L-alanine (L-Dopa) using Erwinia herbicola cells carrying a mutant transcriptional regulator TyrR.
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18715865 D.Milić, T.V.Demidkina, N.G.Faleev, D.Matković-Calogović, and A.A.Antson (2008).
Insights into the catalytic mechanism of tyrosine phenol-lyase from X-ray structures of quinonoid intermediates.
  J Biol Chem, 283, 29206-29214.
PDB codes: 2vlf 2vlh
18094472 M.N.Isupov, and A.A.Lebedev (2008).
NCS-constrained exhaustive search using oligomeric models.
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17937401 O.Almog, A.Kogan, M.Leeuw, G.Y.Gdalevsky, R.Cohen-Luria, and A.H.Parola (2008).
Structural insights into cold inactivation of tryptophanase and cold adaptation of subtilisin S41.
  Biopolymers, 89, 354-359.  
16768450 D.Milić, D.Matković-Calogović, T.V.Demidkina, V.V.Kulikova, N.I.Sinitzina, and A.A.Antson (2006).
Structures of apo- and holo-tyrosine phenol-lyase reveal a catalytically critical closed conformation and suggest a mechanism for activation by K+ ions.
  Biochemistry, 45, 7544-7552.
PDB codes: 2ez1 2ez2
17094783 S.G.Lee, S.P.Hong, d.o. .Y.Kim, J.J.Song, H.S.Ro, and M.H.Sung (2006).
Inactivation of tyrosine phenol-lyase by Pictet-Spengler reaction and alleviation by T15A mutation on intertwined N-terminal arm.
  FEBS J, 273, 5564-5573.  
16790938 S.Y.Ku, P.Yip, and P.L.Howell (2006).
Structure of Escherichia coli tryptophanase.
  Acta Crystallogr D Biol Crystallogr, 62, 814-823.
PDB code: 2c44
16215823 T.Koyanagi, T.Katayama, A.Hirao, H.Suzuki, and H.Kumagai (2005).
Construction of an effective protein expression system using the tpl promoter in Escherichia coli.
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15044726 B.Pioselli, S.Bettati, T.V.Demidkina, L.N.Zakomirdina, R.S.Phillips, and A.Mozzarelli (2004).
Tyrosine phenol-lyase and tryptophan indole-lyase encapsulated in wet nanoporous silica gels: Selective stabilization of tertiary conformations.
  Protein Sci, 13, 913-924.  
15560798 N.G.Faleev, T.V.Demidkina, M.A.Tsvetikova, R.S.Phillips, and I.A.Yamskov (2004).
The mechanism of alpha-proton isotope exchange in amino acids catalysed by tyrosine phenol-lyase. What is the role of quinonoid intermediates?
  Eur J Biochem, 271, 4565-4571.  
12833548 K.Cox, T.Watson, P.Soultanas, and J.D.Hirst (2003).
Molecular dynamics simulations of a helicase.
  Proteins, 52, 254-262.  
11934889 R.S.Phillips, T.V.Demidkina, L.N.Zakomirdina, S.Bruno, L.Ronda, and A.Mozzarelli (2002).
Crystals of tryptophan indole-lyase and tyrosine phenol-lyase form stable quinonoid complexes.
  J Biol Chem, 277, 21592-21597.  
11933244 K.Soda, T.Yoshimura, and N.Esaki (2001).
Stereospecificity for the hydrogen transfer of pyridoxal enzyme reactions.
  Chem Rec, 1, 373-384.  
11737206 R.Contestabile, A.Paiardini, S.Pascarella, M.L.di Salvo, S.D'Aguanno, and F.Bossa (2001).
l-Threonine aldolase, serine hydroxymethyltransferase and fungal alanine racemase. A subgroup of strictly related enzymes specialized for different functions.
  Eur J Biochem, 268, 6508-6525.  
10673430 G.Schneider, H.Käck, and Y.Lindqvist (2000).
The manifold of vitamin B6 dependent enzymes.
  Structure, 8, R1-R6.  
11082202 N.G.Faleev, Y.N.Zhukov, E.N.Khurs, O.I.Gogoleva, M.V.Barbolina, N.P.Bazhulina, V.M.Belikov, T.V.Demidkina, and R.M.Khomutov (2000).
Interaction of tyrosine phenol-lyase with phosphoroorganic analogues of substrate amino acids.
  Eur J Biochem, 267, 6897-6902.  
10712616 N.P.Bazhulina, Y.V.Morozov, A.I.Papisova, and T.V.Demidkina (2000).
Pyridoxal 5'-phoshate schiff base in Citrobacter freundii tyrosinephenol-lyase. Ionic and tautomeric equilibria.
  Eur J Biochem, 267, 1830-1836.  
10684605 T.Fujii, M.Maeda, H.Mihara, T.Kurihara, N.Esaki, and Y.Hata (2000).
Structure of a NifS homologue: X-ray structure analysis of CsdB, an Escherichia coli counterpart of mammalian selenocysteine lyase.
  Biochemistry, 39, 1263-1273.
PDB code: 1c0n
10378276 A.D.Kern, M.A.Oliveira, P.Coffino, and M.L.Hackert (1999).
Structure of mammalian ornithine decarboxylase at 1.6 A resolution: stereochemical implications of PLP-dependent amino acid decarboxylases.
  Structure, 7, 567-581.
PDB code: 7odc
9880502 B.Mouratou, P.Kasper, H.Gehring, and P.Christen (1999).
Conversion of tyrosine phenol-lyase to dicarboxylic amino acid beta-lyase, an enzyme not found in nature.
  J Biol Chem, 274, 1320-1325.  
10353823 E.Woehl, and M.F.Dunn (1999).
Mechanisms of monovalent cation action in enzyme catalysis: the tryptophan synthase alpha-, beta-, and alpha beta-reactions.
  Biochemistry, 38, 7131-7141.  
10212273 H.Ogawa, F.Takusagawa, K.Wakaki, H.Kishi, M.R.Eskandarian, M.Kobayashi, T.Date, N.H.Huh, and H.C.Pitot (1999).
Rat liver serine dehydratase. Bacterial expression and two folding domains as revealed by limited proteolysis.
  J Biol Chem, 274, 12855-12860.  
10387080 J.N.Scarsdale, G.Kazanina, S.Radaev, V.Schirch, and H.T.Wright (1999).
Crystal structure of rabbit cytosolic serine hydroxymethyltransferase at 2.8 A resolution: mechanistic implications.
  Biochemistry, 38, 8347-8358.
PDB code: 1cj0
9521672 J.Gong, G.A.Hunter, and G.C.Ferreira (1998).
Aspartate-279 in aminolevulinate synthase affects enzyme catalysis through enhancing the function of the pyridoxal 5'-phosphate cofactor.
  Biochemistry, 37, 3509-3517.  
9914259 J.N.Jansonius (1998).
Structure, evolution and action of vitamin B6-dependent enzymes.
  Curr Opin Struct Biol, 8, 759-769.  
9837895 K.D.Schnackerz, and A.Mozzarelli (1998).
Plasticity of the tryptophan synthase active site probed by 31P NMR spectroscopy.
  J Biol Chem, 273, 33247-33253.  
9565551 K.H.Jhee, L.H.Yang, S.A.Ahmed, P.McPhie, R.Rowlett, and E.W.Miles (1998).
Mutation of an active site residue of tryptophan synthase (beta-serine 377) alters cofactor chemistry.
  J Biol Chem, 273, 11417-11422.  
9772188 K.H.Jhee, P.McPhie, H.S.Ro, and E.W.Miles (1998).
Tryptophan synthase mutations that alter cofactor chemistry lead to mechanism-based inactivation.
  Biochemistry, 37, 14591-14604.  
  9422600 K.Martin, G.Morlin, A.Smith, A.Nordyke, A.Eisenstark, and M.Golomb (1998).
The tryptophanase gene cluster of Haemophilus influenzae type b: evidence for horizontal gene transfer.
  J Bacteriol, 180, 107-118.  
  9605314 K.Qu, D.L.Martin, and C.E.Lawrence (1998).
Motifs and structural fold of the cofactor binding site of human glutamate decarboxylase.
  Protein Sci, 7, 1092-1105.  
  9829925 Q.Bai, and R.L.Somerville (1998).
Integration host factor and cyclic AMP receptor protein are required for TyrR-mediated activation of tpl in Citrobacter freundii.
  J Bacteriol, 180, 6173-6186.  
9753690 S.B.Renwick, K.Snell, and U.Baumann (1998).
The crystal structure of human cytosolic serine hydroxymethyltransferase: a target for cancer chemotherapy.
  Structure, 6, 1105-1116.
PDB code: 1bj4
  10082378 S.Ishii, H.Hayashi, A.Okamoto, and H.Kagamiyama (1998).
Aromatic L-amino acid decarboxylase: conformational change in the flexible region around Arg334 is required during the transaldimination process.
  Protein Sci, 7, 1802-1810.  
  9761478 S.Pascarella, S.Angelaccio, R.Contestabile, S.Delle Fratte, M.Di Salvo, and F.Bossa (1998).
The structure of serine hydroxymethyltransferase as modeled by homology and validated by site-directed mutagenesis.
  Protein Sci, 7, 1976-1982.  
9188741 A.V.Efimov (1997).
Structural trees for protein superfamilies.
  Proteins, 28, 241-260.  
9354624 H.Hayashi, and H.Kagamiyama (1997).
Transient-state kinetics of the reaction of aspartate aminotransferase with aspartate at low pH reveals dual routes in the enzyme-substrate association process.
  Biochemistry, 36, 13558-13569.  
  9294452 H.Q.Smith, and R.L.Somerville (1997).
The tpl promoter of Citrobacter freundii is activated by the TyrR protein.
  J Bacteriol, 179, 5914-5921.  
9063881 J.P.Shaw, G.A.Petsko, and D.Ringe (1997).
Determination of the structure of alanine racemase from Bacillus stearothermophilus at 1.9-A resolution.
  Biochemistry, 36, 1329-1342.
PDB code: 1sft
9249049 J.R.Jagath, B.Sharma, B.Bhaskar, A.Datta, N.A.Rao, and H.S.Savithri (1997).
Importance of the amino terminus in maintenance of oligomeric structure of sheep liver cytosolic serine hydroxymethyltransferase.
  Eur J Biochem, 247, 372-379.  
9346293 M.Kataoka, M.Ikemi, T.Morikawa, T.Miyoshi, K.Nishi, M.Wada, H.Yamada, and S.Shimizu (1997).
Isolation and characterization of D-threonine aldolase, a pyridoxal-5'-phosphate-dependent enzyme from Arthrobacter sp. DK-38.
  Eur J Biochem, 248, 385-393.  
  9300500 P.Dominici, P.S.Moore, S.Castellani, M.Bertoldi, and C.B.Voltattorni (1997).
Mutation of cysteine 111 in Dopa decarboxylase leads to active site perturbation.
  Protein Sci, 6, 2007-2015.  
9119037 R.S.Phillips, R.L.Von Tersch, and F.Secundo (1997).
Effects of tyrosine ring fluorination on rates and equilibria of formation of intermediates in the reactions of carbon-carbon lyases.
  Eur J Biochem, 244, 658-663.  
8916896 J.Gong, C.J.Kay, M.J.Barber, and G.C.Ferreira (1996).
Mutations at a glycine loop in aminolevulinate synthase affect pyridoxal phosphate cofactor binding and catalysis.
  Biochemistry, 35, 14109-14117.  
  7663340 C.Momany, R.Ghosh, and M.L.Hackert (1995).
Structural motifs for pyridoxal-5'-phosphate binding in decarboxylases: an analysis based on the crystal structure of the Lactobacillus 30a ornithine decarboxylase.
  Protein Sci, 4, 849-854.  
7744078 H.Chen, P.Gollnick, and R.S.Phillips (1995).
Site-directed mutagenesis of His343-->Ala in Citrobacter freundii tyrosine phenol-lyase. Effects on the kinetic mechanism and rate-determining step.
  Eur J Biochem, 229, 540-549.  
  7670372 N.V.Grishin, M.A.Phillips, and E.J.Goldsmith (1995).
Modeling of the spatial structure of eukaryotic ornithine decarboxylases.
  Protein Sci, 4, 1291-1304.  
7615535 S.B.Ruvinov, S.A.Ahmed, P.McPhie, and E.W.Miles (1995).
Monovalent cations partially repair a conformational defect in a mutant tryptophan synthase alpha 2 beta 2 complex (beta-E109A).
  J Biol Chem, 270, 17333-17338.  
8112347 F.W.Alexander, E.Sandmeier, P.K.Mehta, and P.Christen (1994).
Evolutionary relationships among pyridoxal-5'-phosphate-dependent enzymes. Regio-specific alpha, beta and gamma families.
  Eur J Biochem, 219, 953-960.  
7925461 S.Delle Fratte, S.Iurescia, S.Angelaccio, F.Bossa, and V.Schirch (1994).
The function of arginine 363 as the substrate carboxyl-binding site in Escherichia coli serine hydroxymethyltransferase.
  Eur J Biochem, 225, 395-401.  
  8003988 S.Pascarella, and F.Bossa (1994).
Similarity between pyridoxal/pyridoxamine phosphate-dependent enzymes involved in dideoxy and deoxyaminosugar biosynthesis and other pyridoxal phosphate enzymes.
  Protein Sci, 3, 701-705.  
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