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PDBsum entry 1t6j

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protein ligands Protein-protein interface(s) links
Lyase PDB id
1t6j
Jmol
Contents
Protein chains
647 a.a. *
Ligands
CIN
Waters ×411
* Residue conservation analysis
PDB id:
1t6j
Name: Lyase
Title: Crystal structure of phenylalanine ammonia lyase from rhodos toruloides
Structure: Phenylalanine ammonia-lyase. Chain: a, b. Engineered: yes
Source: Rhodosporidium toruloides. Organism_taxid: 5286. Gene: pal. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
Resolution:
2.10Å     R-factor:   0.243     R-free:   0.298
Authors: J.C.Calabrese,D.B.Jordan
Key ref:
J.C.Calabrese et al. (2004). Crystal structure of phenylalanine ammonia lyase: multiple helix dipoles implicated in catalysis. Biochemistry, 43, 11403-11416. PubMed id: 15350127 DOI: 10.1021/bi049053+
Date:
06-May-04     Release date:   12-Oct-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P11544  (PALY_RHOTO) -  Phenylalanine/tyrosine ammonia-lyase
Seq:
Struc:
 
Seq:
Struc:
716 a.a.
647 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.4.3.1.25  - Phenylalanine/tyrosine ammonia-lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. L-phenylalanine = trans-cinnamate + ammonia
2. L-tyrosine = trans-p-hydroxycinnamate + ammonia
L-phenylalanine
=
trans-cinnamate
Bound ligand (Het Group name = CIN)
corresponds exactly
+ ammonia
L-tyrosine
= trans-p-hydroxycinnamate
+ ammonia
      Cofactor: MIO
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     biosynthetic process   4 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi049053+ Biochemistry 43:11403-11416 (2004)
PubMed id: 15350127  
 
 
Crystal structure of phenylalanine ammonia lyase: multiple helix dipoles implicated in catalysis.
J.C.Calabrese, D.B.Jordan, A.Boodhoo, S.Sariaslani, T.Vannelli.
 
  ABSTRACT  
 
The first three-dimensional structure of phenylalanine ammonia lyase (PAL) has been determined at 2.1 A resolution for PAL from Rhodosporidium toruloides. The enzyme is structurally similar to the mechanistically related histidine ammonia lyase (HAL), with PAL having an additional approximately 160 residues extending from the common fold. We propose that catalysis (including lowering the pK(a) of nonacidic C3 of l-phenylalanine for an E1cb mechanism) is potentially governed by dipole moments of seven alpha helices associated with the PAL active site (six positive poles and one negative pole). Cofactor 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) resides atop the positive poles of three helices, for increasing its electrophilicity. The helix dipoles appear fully compatible with a model of phenylalanine docked in the active site of PAL having the first covalent bond formed between the amino group of substrate and the methylidene group of MIO: 12 highly conserved residues (near the N termini of helices for enhancing function) are poised to serve roles in substrate recognition, MIO activation, product separation, proton donation, or polarizing electrons from the phenyl ring of substrate for activation of C3; and a highly conserved His residue (near the C terminus of the one helix that directs its negative pole toward the active site to increase the residue's basicity) is positioned to act as a general base, abstracting the pro-S hydrogen from C3 of substrate. A similar mechanism is proposed for HAL, which has a similar disposition of seven alpha helices and similar active-site residues. The helix dipoles appear incompatible with a proposed mechanism that invokes a carbocation intermediate.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21131229 N.J.Turner (2011).
Ammonia lyases and aminomutases as biocatalysts for the synthesis of α-amino and β-amino acids.
  Curr Opin Chem Biol, 15, 234-240.  
21052759 X.Wang (2011).
Structure, function, and engineering of enzymes in isoflavonoid biosynthesis.
  Funct Integr Genomics, 11, 13-22.  
20577998 H.A.Cooke, and S.D.Bruner (2010).
Probing the active site of MIO-dependent aminomutases, key catalysts in the biosynthesis of beta-amino acids incorporated in secondary metabolites.
  Biopolymers, 93, 802-810.
PDB codes: 3kdy 3kdz
19364318 A.A.Pakhomov, and V.I.Martynov (2009).
Posttranslational chemistry of proteins of the GFP family.
  Biochemistry (Mosc), 74, 250-259.  
19123196 B.Wu, W.Szymanski, P.Wietzes, S.de Wildeman, G.J.Poelarends, B.L.Feringa, and D.B.Janssen (2009).
Enzymatic Synthesis of Enantiopure alpha- and beta-Amino Acids by Phenylalanine Aminomutase-Catalysed Amination of Cinnamic Acid Derivatives.
  Chembiochem, 10, 338-344.  
19222035 D.Krug, and R.Müller (2009).
Discovery of additional members of the tyrosine aminomutase enzyme family and the mutational analysis of CmdF.
  Chembiochem, 10, 741-750.  
19620019 H.A.Cooke, C.V.Christianson, and S.D.Bruner (2009).
Structure and chemistry of 4-methylideneimidazole-5-one containing enzymes.
  Curr Opin Chem Biol, 13, 460-468.  
18454352 J.Song, and Z.Wang (2009).
Molecular cloning, expression and characterization of a phenylalanine ammonia-lyase gene (SmPAL1) from Salvia miltiorrhiza.
  Mol Biol Rep, 36, 939-952.  
19082600 S.McInnis, S.Clemens, and A.R.Kermode (2009).
The ornamental variety, Japanese striped corn, contains high anthocyanin levels and PAL specific activity: establishing the potential for development of an oral therapeutic.
  Plant Cell Rep, 28, 503-515.  
19095795 C.N.Sarkissian, A.Gámez, L.Wang, M.Charbonneau, P.Fitzpatrick, J.F.Lemontt, B.Zhao, M.Vellard, S.M.Bell, C.Henschell, A.Lambert, L.Tsuruda, R.C.Stevens, and C.R.Scriver (2008).
Preclinical evaluation of multiple species of PEGylated recombinant phenylalanine ammonia lyase for the treatment of phenylketonuria.
  Proc Natl Acad Sci U S A, 105, 20894-20899.  
19030603 L.B.Davin, M.Jourdes, A.M.Patten, K.W.Kim, D.G.Vassão, and N.G.Lewis (2008).
Dissection of lignin macromolecular configuration and assembly: Comparison to related biochemical processes in allyl/propenyl phenol and lignan biosynthesis.
  Nat Prod Rep, 25, 1015-1090.  
18556022 L.Wang, A.Gamez, H.Archer, E.E.Abola, C.N.Sarkissian, P.Fitzpatrick, D.Wendt, Y.Zhang, M.Vellard, J.Bliesath, S.M.Bell, J.F.Lemontt, C.R.Scriver, and R.C.Stevens (2008).
Structural and biochemical characterization of the therapeutic Anabaena variabilis phenylalanine ammonia lyase.
  J Mol Biol, 380, 623-635.
PDB code: 3czo
  19079566 N.P.Lemay, A.L.Morgan, E.J.Archer, L.A.Dickson, C.M.Megley, and M.Zimmer (2008).
The Role of the Tight-Turn, Broken Hydrogen Bonding, Glu222 and Arg96 in the Post-translational Green Fluorescent Protein Chromophore Formation.
  Chem Phys, 348, 152-160.  
17456010 F.S.Sariaslani (2007).
Development of a combined biological and chemical process for production of industrial aromatics from renewable resources.
  Annu Rev Microbiol, 61, 51-69.  
17240984 M.C.Moffitt, G.V.Louie, M.E.Bowman, J.Pence, J.P.Noel, and B.S.Moore (2007).
Discovery of two cyanobacterial phenylalanine ammonia lyases: kinetic and structural characterization.
  Biochemistry, 46, 1004-1012.
PDB codes: 2nyf 2nyn
17612622 M.J.MacDonald, and G.B.D'Cunha (2007).
A modern view of phenylalanine ammonia lyase.
  Biochem Cell Biol, 85, 273-282.  
17545150 S.Rachid, D.Krug, K.J.Weissman, and R.Müller (2007).
Biosynthesis of (R)-beta-tyrosine and its incorporation into the highly cytotoxic chondramides produced by Chondromyces crocatus.
  J Biol Chem, 282, 21810-21817.  
17602252 Z.Xue, M.McCluskey, K.Cantera, F.S.Sariaslani, and L.Huang (2007).
Identification, characterization and functional expression of a tyrosine ammonia-lyase and its mutants from the photosynthetic bacterium Rhodobacter sphaeroides.
  J Ind Microbiol Biotechnol, 34, 599-604.  
16419141 C.Paizs, A.Katona, and J.Rétey (2006).
The interaction of heteroaryl-acrylates and alanines with phenylalanine ammonia-lyase from parsley.
  Chemistry, 12, 2739-2744.  
17185228 G.V.Louie, M.E.Bowman, M.C.Moffitt, T.J.Baiga, B.S.Moore, and J.P.Noel (2006).
Structural determinants and modulation of substrate specificity in phenylalanine-tyrosine ammonia-lyases.
  Chem Biol, 13, 1327-1338.
PDB codes: 2o6y 2o78 2o7b 2o7d 2o7e 2o7f
17185227 K.T.Watts, B.N.Mijts, P.C.Lee, A.J.Manning, and C.Schmidt-Dannert (2006).
Discovery of a substrate selectivity switch in tyrosine ammonia-lyase, a member of the aromatic amino acid lyase family.
  Chem Biol, 13, 1317-1326.  
16547054 M.Berner, D.Krug, C.Bihlmaier, A.Vente, R.Müller, and A.Bechthold (2006).
Genes and enzymes involved in caffeic acid biosynthesis in the actinomycete Saccharothrix espanaensis.
  J Bacteriol, 188, 2666-2673.  
16478474 S.Pilbák, A.Tomin, J.Rétey, and L.Poppe (2006).
The essential tyrosine-containing loop conformation and the role of the C-terminal multi-helix region in eukaryotic phenylalanine ammonia-lyases.
  FEBS J, 273, 1004-1019.  
16267872 C.T.Walsh, S.Garneau-Tsodikova, and G.J.Gatto (2005).
Protein posttranslational modifications: the chemistry of proteome diversifications.
  Angew Chem Int Ed Engl, 44, 7342-7372.  
15860421 J.P.Noel, M.B.Austin, and E.K.Bomati (2005).
Structure-function relationships in plant phenylpropanoid biosynthesis.
  Curr Opin Plant Biol, 8, 249-253.  
17193201 J.Zoń, P.Miziak, N.Amrhein, and R.Gancarz (2005).
Inhibitors of phenylalanine ammonia-lyase (PAL): synthesis and biological evaluation of 5-substituted 2-aminoindane-2-phosphonic acids.
  Chem Biodivers, 2, 1187-1194.  
15824922 K.Nijkamp, N.van Luijk, J.A.de Bont, and J.Wery (2005).
The solvent-tolerant Pseudomonas putida S12 as host for the production of cinnamic acid from glucose.
  Appl Microbiol Biotechnol, 69, 170-177.  
15937191 L.Xiang, and B.S.Moore (2005).
Biochemical characterization of a prokaryotic phenylalanine ammonia lyase.
  J Bacteriol, 187, 4286-4289.  
16121398 O.Koch, M.Bocola, and G.Klebe (2005).
Cooperative effects in hydrogen-bonding of protein secondary structure elements: a systematic analysis of crystal data using Secbase.
  Proteins, 61, 310-317.  
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 codes are shown on the right.