DB code: D00258

CATH domain 3.90.1150.10 : Aspartate Aminotransferase, domain 1 Catalytic domain
3.40.640.10 : Aspartate Aminotransferase; domain 2 Catalytic domain
E.C. 4.1.99.2
CSA 2tpl
M-CSA 2tpl
MACiE

CATH domain Related DB codes (homologues)
3.90.1150.10 : Aspartate Aminotransferase, domain 1 D00085 D00092 D00101 D00102 D00103 D00104 D00107 D00108 D00109 D00255 D00257 D00265 D00269 D00515 M00031 D00279
3.40.640.10 : Aspartate Aminotransferase; domain 2 D00085 D00092 D00101 D00102 D00103 D00104 D00107 D00108 D00109 D00255 D00257 D00265 D00269 D00515 M00031 D00279

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
P31013 Tyrosine phenol-lyase
EC 4.1.99.2
Beta-tyrosinase
PF01212 (Beta_elim_lyase)
[Graphical View]
P31012 Tyrosine phenol-lyase
EC 4.1.99.2
Beta-tyrosinase
PF01212 (Beta_elim_lyase)
[Graphical View]

KEGG enzyme name
tyrosine phenol-lyase
beta-tyrosinase
L-tyrosine phenol-lyase (deaminating)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P31012 TPL_ESCIN L-tyrosine + H(2)O = phenol + pyruvate + NH(3). Homotetramer. Pyridoxal phosphate.
P31013 TPL_CITFR L-tyrosine + H(2)O = phenol + pyruvate + NH(3). Homotetramer. Pyridoxal phosphate.

KEGG Pathways
Map code Pathways E.C.
MAP00910 Nitrogen metabolism
MAP00350 Tyrosine metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00018 C00082 C00001 C00146 C00022 C00014
E.C.
Compound Pyridoxal phosphate L-Tyrosine H2O Phenol Pyruvate NH3
Type aromatic ring (with nitrogen atoms),phosphate group/phosphate ion amino acids,aromatic ring (only carbon atom) H2O aromatic ring (only carbon atom) carbohydrate,carboxyl group amine group,organic ion
ChEBI 18405
58315
17895
15377
15882
32816
16134
PubChem 1051
6942100
6057
962
22247451
996
20488062
1060
222
1tplA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1tplB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
2tplA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
2tplB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:HPP Unbound Unbound Unbound
1tplA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1tplB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
2tplA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
2tplB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [10], [12], [16] & [18]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1tplA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 381 GLY 52(Monovalent cation)
1tplB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 381 GLY 52(Monovalent cation)
2tplA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 381 GLY 52(Monovalent cation)
2tplB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 381 GLY 52(Monovalent cation)
1tplA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 71; ;LYS 257 GLU 69;ASN 262(Monovalent cation) invisible 123-131
1tplB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 71; ;LYS 257 GLU 69;ASN 262(Monovalent cation) invisible 123-131
2tplA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 71;THR 124; GLU 69;ASN 262(Monovalent cation) LLP 257(Modified by PLP) LLP(modified Lys)
2tplB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 71;THR 124; GLU 69;ASN 262(Monovalent cation) LLP 257(Modified by PLP) LLP(modified Lys)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[6]
Scheme 1, Scheme 2, p.399-401 3
[10]
Scheme 2, p.12282-12283 6
[12]
Scheme 1, p.6509-6510 6
[14]
SCHEME1, p.1324-1325 5
[15]
Scheme 1, p.8555 4
[16]
Scheme 1, p.6899-6900 7
[18]
Scheme 3, p.751-752 5
[19]
SCHEME 3

References
[1]
Resource
Comments
Medline ID
PubMed ID 1190012
Journal Adv Appl Microbiol
Year 1975
Volume 19
Pages 249-88
Authors Yamada H, Kumagai H
Title Synthesis of L-tyrosine-related amino acids by beta-tyrosinase.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 1147922
Journal Biochem Biophys Res Commun
Year 1975
Volume 64
Pages 241-7
Authors Rapp P, Kumagai H, Yamada H, Ueno T, Fukami H
Title Synthesis of 2,3,4-trihydroxy-L-phenylalanine from s-methyl-L-cysteine and pyrogallol by L-tyrosine phenol-lyase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 1141596
Journal J Am Chem Soc
Year 1975
Volume 97
Pages 4334-7
Authors Sawada S, Kumagai H, Yamada H, Hill RK
Title Stereochemistry of beta-replacement reactions catalyzed by tyrosine phenol-lyase.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 721797
Journal J Biochem (Tokyo)
Year 1978
Volume 84
Pages 633-40
Authors Muro T, Nakatani H, Hiromi K, Kumagai H, Yamada H
Title Elementary processes in the interaction of tyrosine phenol lyase with inhibitors and substrate.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 3111376
Journal Arch Biochem Biophys
Year 1987
Volume 256
Pages 302-10
Authors Phillips RS
Title Reactions of O-acyl-L-serines with tryptophanase, tyrosine phenol-lyase, and tryptophan synthase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 2847927
Journal Eur J Biochem
Year 1988
Volume 177
Pages 395-401
Authors Faleev NG, Ruvinov SB, Demidkina TV, Myagkikh IV, Gololobov MYu, Bakhmutov VI, Belikov VM
Title Tyrosine phenol-lyase from Citrobacter intermedius. Factors controlling substrate specificity.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 3378628
Journal FEBS Lett
Year 1988
Volume 232
Pages 381-2
Authors Demidkina TV, Myagkikh IV, Antson AA, Harutyunyan EH
Title Crystallization and crystal data on tyrosine phenol-lyase.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
Medline ID 92290010
PubMed ID 1601133
Journal FEBS Lett
Year 1992
Volume 302
Pages 256-60
Authors Antson AA, Strokopytov BV, Murshudov GN, Isupov MN, Harutyunyan EH, Demidkina TV, Vassylyev DG, Dauter Z, Terry H, Wilson KS
Title The polypeptide chain fold in tyrosine phenol-lyase, a pyridoxal-5'-phosphate-dependent enzyme.
Related PDB
Related UniProtKB P31013
[9]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 7916622
Journal Biochemistry
Year 1993
Volume 32
Pages 4195-206
Authors Antson AA, Demidkina TV, Gollnick P, Dauter Z, von Tersch RL, Long J, Berezhnoy SN, Phillips RS, Harutyunyan EH, Wilson KS
Title Three-dimensional structure of tyrosine phenol-lyase.
Related PDB 1tpl
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 7547970
Journal Biochemistry
Year 1995
Volume 34
Pages 12276-83
Authors Chen HY, Demidkina TV, Phillips RS
Title Site-directed mutagenesis of tyrosine-71 to phenylalanine in Citrobacter freundii tyrosine phenol-lyase: evidence for dual roles of tyrosine-71 as a general acid catalyst in the reaction mechanism and in cofactor binding.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 8932517
Journal Biochem Mol Biol Int
Year 1996
Volume 38
Pages 37-42
Authors Pletnev SV, Isupov MN, Dauter Z, Wilson KS, Faleev NG, Harutyunyan EG, Demidkina TV
Title Purification and crystals of tyrosine phenol-lyase from Erwinia herbicola.
Related PDB
Related UniProtKB
[12]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID 97317094
PubMed ID 9174368
Journal Biochemistry
Year 1997
Volume 36
Pages 6502-10
Authors Sundararaju B, Antson AA, Phillips RS, Demidkina TV, Barbolina MV, Gollnick P, Dodson GG, Wilson KS
Title The crystal structure of Citrobacter freundii tyrosine phenol-lyase complexed with 3-(4'-hydroxyphenyl)propionic acid, together with site-directed mutagenesis and kinetic analysis, demonstrates that arginine 381 is required for substrate specificity.
Related PDB 2tpl
Related UniProtKB P31013
[13]
Resource
Comments
Medline ID
PubMed ID 10328314
Journal Bioorg Med Chem Lett
Year 1999
Volume 9
Pages 1205-8
Authors Kim K, Cole PA
Title Synthesis of (2S,3R)-beta-methyltyrosine catalyzed by tyrosine phenol-lyase.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 9880502
Journal J Biol Chem
Year 1999
Volume 274
Pages 1320-5
Authors Mouratou B, Kasper P, Gehring H, Christen P
Title Conversion of tyrosine phenol-lyase to dicarboxylic amino acid beta-lyase, an enzyme not found in nature.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 10913261
Journal Biochemistry
Year 2000
Volume 39
Pages 8546-55
Authors Sundararaju B, Chen H, Shilcutt S, Phillips RS
Title The role of glutamic acid-69 in the activation of Citrobacter freundii tyrosine phenol-lyase by monovalent cations.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 11082202
Journal Eur J Biochem
Year 2000
Volume 267
Pages 6897-902
Authors Faleev NG, Zhukov YN, Khurs EN, Gogoleva OI, Barbolina MV, Bazhulina NP, Belikov VM, Demidkina TV, Khomutov RM
Title Interaction of tyrosine phenol-lyase with phosphoroorganic analogues of substrate amino acids.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 11732906
Journal Biochemistry
Year 2001
Volume 40
Pages 14862-8
Authors Watkins EB, Phillips RS
Title Inhibition of tyrosine phenol-lyase from Citrobacter freundii by 2-azatyrosine and 3-azatyrosine.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 11964175
Journal Biochem J
Year 2002
Volume 363
Pages 745-52
Authors Demidkina TV, Barbolina MV, Faleev NG, Sundararaju B, Gollnick PD, Phillips RS
Title Threonine-124 and phenylalanine-448 in Citrobacter freundii tyrosine phenol-lyase are necessary for activity with L-tyrosine.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 11934889
Journal J Biol Chem
Year 2002
Volume 277
Pages 21592-7
Authors Phillips RS, Demidkina TV, Zakomirdina LN, Bruno S, Ronda L, Mozzarelli A
Title Crystals of tryptophan indole-lyase and tyrosine phenol-lyase form stable quinonoid complexes.
Related PDB
Related UniProtKB

Comments
This enzyme catalyzes several reactions;
(A) Formation of external aldimine from internal aldimine (with pyridoxal phosphate;PLP) involves addition to double-bond and elimination accompanied by double-bond formation. (Arg217 can be involved in the formation.)
(B) Elimination of phenol, accompanied by double-bond formation.
(C) Return to internal aldimine involves addition to double-bond, and elimination accompanied by double-bond formation.
(D) Hydrolysis of aldimine bond.
However, the mechanism of hydrolysis has not been elucidated.

Created Updated
2004-07-01 2009-02-26