D00539
type: Enzyme
rlcp: p63
cath: http://ezcatdb.cbrc.jp/EzCatDB/cath/3.40.-.-
cath: Rossmann fold
ec: https://purl.uniprot.org/enzyme/3.3.2.10
uniprot: P34914
kegg enzyme: soluble epoxide hydrolase
kegg enzyme: epoxide hydrase (ambiguous)
kegg enzyme: epoxide hydratase (ambiguous)
kegg enzyme: arene-oxide hydratase (ambiguous)
kegg enzyme: aryl epoxide hydrase (ambiguous)
kegg enzyme: trans-stilbene oxide hydrolase
kegg enzyme: sEH
kegg enzyme: cytosolic epoxide hydrolase
kegg pathway: Arachidonic acid metabolism
kegg pathway: Tetrachloroethene degradation
kegg substrate: Epoxide
kegg substrate: Arene oxide
kegg substrate: H2O
kegg product: Glycol
kegg product: Arene diol
pdb: 1cqzA01
pdb: 1cqzB01
pdb: 1cr6A01
pdb: 1cr6B01
pdb: 1ek1A01
pdb: 1ek1B01
pdb: 1ek2A01
pdb: 1ek2B01
pdb: 1cqzA02
pdb: 1cqzB02
pdb: 1cr6A02
pdb: 1cr6B02
pdb: 1ek1A02
pdb: 1ek1B02
pdb: 1ek2A02
pdb: 1ek2B02
pdb bound state: Unbound
  compound: Epoxide
  pdb: 1cqzA01
pdb bound state: Unbound
  compound: Epoxide
  pdb: 1cqzB01
pdb bound state: Unbound
  compound: Epoxide
  pdb: 1cr6A01
pdb bound state: Unbound
  compound: Epoxide
  pdb: 1cr6B01
pdb bound state: Unbound
  compound: Epoxide
  pdb: 1ek1A01
pdb bound state: Unbound
  compound: Epoxide
  pdb: 1ek1B01
pdb bound state: Unbound
  compound: Epoxide
  pdb: 1ek2A01
pdb bound state: Unbound
  compound: Epoxide
  pdb: 1ek2B01
pdb bound state: Unbound
  compound: Epoxide
  pdb: 1cqzA02
pdb bound state: Unbound
  compound: Epoxide
  pdb: 1cqzB02
pdb bound state: Analogue
  compound: Epoxide
  pdb: 1cr6A02
  ligand het code: CPU
active site residues resources: Structure of Aspergillus niger epoxide hydrolase at 1.8 A resolution: implications for the structure and function of the mammalian microsomal class of epoxide hydrolases.
active site residues resources: Binding of alkylurea inhibitors to epoxide hydrolase implicates active site tyrosines in substrate activation.
active site residues resources: Biochemical evidence for the involvement of tyrosine in epoxide activation during the catalytic cycle of epoxide hydrolase.
active site residues resources: Tyrosine residues serve as proton donor in the catalytic mechanism of epoxide hydrolase from Agrobacterium radiobacter.
active site residues resources: Identification and functional characterization of human soluble epoxide hydrolase genetic polymorphisms.
references: Identification and functional characterization of human soluble epoxide hydrolase genetic polymorphisms.
references: Molecular and biochemical evidence for the involvement of the Asp-333-His-523 pair in the catalytic mechanism of soluble epoxide hydrolase.
references: Mechanism of soluble epoxide hydrolase. Formation of an alpha-hydroxy ester-enzyme intermediate through Asp-333.
references: Asp333, Asp495, and His523 form the catalytic triad of rat soluble epoxide hydrolase.
references: Primary structure and catalytic mechanism of the epoxide hydrolase from Agrobacterium radiobacter AD1.
references: Mechanism of microsomal epoxide hydrolase. Semifunctional site-specific mutants affecting the alkylation half-reaction.
references: Semifunctional site-specific mutants affecting the hydrolytic half-reaction of microsomal epoxide hydrolase.
references: Characterisation of a catabolic epoxide hydrolase from a Corynebacterium sp.
references: Catalytic triad of microsomal epoxide hydrolase: replacement of Glu404 with Asp leads to a strongly increased turnover rate.
references: Kinetic mechanism of the enantioselective conversion of styrene oxide by epoxide hydrolase from Agrobacterium radiobacter AD1.
references: Epoxide hydrolases and their synthetic applications.
references: Kinetic and chemical mechanism of epoxide hydrolase.
references: The x-ray structure of epoxide hydrolase from Agrobacterium radiobacter AD1. An enzyme to detoxify harmful epoxides.
references: Detoxification of environmental mutagens and carcinogens: structure, mechanism, and evolution of liver epoxide hydrolase.
references: Structure of Aspergillus niger epoxide hydrolase at 1.8 A resolution: implications for the structure and function of the mammalian microsomal class of epoxide hydrolases.
references: Binding of alkylurea inhibitors to epoxide hydrolase implicates active site tyrosines in substrate activation.
references: Biochemical evidence for the involvement of tyrosine in epoxide activation during the catalytic cycle of epoxide hydrolase.
references: Tyrosine residues serve as proton donor in the catalytic mechanism of epoxide hydrolase from Agrobacterium radiobacter.
references: 3-D QSAR analysis of inhibition of murine soluble epoxide hydrolase (MsEH) by benzoylureas, arylureas, and their analogues.
references: New structural and chemical insight into the catalytic mechanism of epoxide hydrolases.
references: A theoretical examination of the acid-catalyzed and noncatalyzed ring-opening reaction of an oxirane by nucleophilic addition of acetate. Implications to epoxide hydrolases.
references: Microbial epoxide hydrolases for preparative biotransformations.
references: Reaction mechanism of soluble epoxide hydrolase: insights from molecular dynamics simulations.
references: Alpha/Beta-hydrolase fold enzymes: structures, functions and mechanisms.
references: Quantitative structure-activity relationships for the enantioselectivity of oxirane ring-opening catalyzed by epoxide hydrolases.
references: Polymorphisms in human soluble epoxide hydrolase.
comment: The E.C. was transferred from 3.3.2.3 to 3.3.2.10. This enzyme belongs to the Alpha/Beta hydrolase superfamily. Moreover, this enzyme is homologous to counterpart enzymes from fungi and bacteria (S00352 in EzCATDB). Although this enzyme binds magnesium ion, it is not involved in catalysis. According to the literature [13], [14], & [15], the catalysis proceeds through an SN2-like reaction. In the first step, Asp333 (PDB 1cqz) makes a nucleophilic attack on the epoxide to form a "glycol-monoester intermediate", whilst Tyr465 and Tyr381 (PDB 1cqz) stablize the negative charged oxygen atom in the transition-state, and act as a general acid catalyst to facilitate the epoxide ring opening, by protonating to the epoxide oxygen. In the second step, the glycol-monoester intermediate is hydrolyzed by a water molecule, which is activated through proton abstraction by the His523/Asp495 (PDB 1cqz) charge-relay system.

Rossmann fold
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.40.50.1820
catalytic domain: index.html

Arachidonic acid metabolism
type: KeggPathway
references: KEGG:MAP00590

Tetrachloroethene degradation
type: KeggPathway
references: KEGG:MAP00625

Epoxide
type: KeggSubstrate
references: KEGG:C00722
compound type: carbohydrate

Arene oxide
type: KeggSubstrate
references: KEGG:C01782
compound type: aromatic ring (only carbon atom)
compound type: carbohydrate
references: CHEBI:2817
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

H2O
type: KeggSubstrate
references: KEGG:C00001
compound type: H2O
references: CHEBI:15377
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Glycol
type: KeggProduct
references: KEGG:C01380
compound type: carbohydrate
references: CHEBI:30742
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Arene diol
type: KeggProduct
references: KEGG:C01666
compound type: aromatic ring (only carbon atom)
compound type: carbohydrate

1cqzA02
type: Pdb
references: 1cqz
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1cqz
catalytic residue: ASP 333;TYR 381;TYR 465;ASP 495;HIS 523

1cqzB02
type: Pdb
references: 1cqz
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1cqz
catalytic residue: ASP 333;TYR 381;TYR 465;ASP 495;HIS 523

1cr6A02
type: Pdb
references: 1cr6
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1cr6
catalytic residue: ASP 333;TYR 381;TYR 465;ASP 495;HIS 523

1cr6B02
type: Pdb
references: 1cr6
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1cr6
catalytic residue: ASP 333;TYR 381;TYR 465;ASP 495;HIS 523

1ek1A02
type: Pdb
references: 1ek1
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ek1
catalytic residue: ASP 333;TYR 381;TYR 465;ASP 495;HIS 523

1ek1B02
type: Pdb
references: 1ek1
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ek1
catalytic residue: ASP 333;TYR 381;TYR 465;ASP 495;HIS 523

1ek2A02
type: Pdb
references: 1ek2
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ek2
catalytic residue: ASP 333;TYR 381;TYR 465;ASP 495;HIS 523

1ek2B02
type: Pdb
references: 1ek2
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ek2
catalytic residue: ASP 333;TYR 381;TYR 465;ASP 495;HIS 523

Identification and functional characterization of human soluble epoxide hydrolase genetic polymorphisms.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10862610
journal: J Biol Chem
volume: 275
pages: 28873-81
published year: 2000
authors:
  item: Sandberg M
  item: Hassett C
  item: Adman ET
  item: Meijer J
  item: Omiecinski CJ

Molecular and biochemical evidence for the involvement of the Asp-333-His-523 pair in the catalytic mechanism of soluble epoxide hydrolase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/7713895
journal: J Biol Chem
volume: 270
pages: 7968-74
published year: 1995
authors:
  item: Pinot F
  item: Grant DF
  item: Beetham JK
  item: Parker AG
  item: Borhan B
  item: Landt S
  item: Jones AD
  item: Hammock BD

Mechanism of soluble epoxide hydrolase. Formation of an alpha-hydroxy ester-enzyme intermediate through Asp-333.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/7592938
journal: J Biol Chem
volume: 270
pages: 26923-30
published year: 1995
authors:
  item: Borhan B
  item: Jones AD
  item: Pinot F
  item: Grant DF
  item: Kurth MJ
  item: Hammock BD

Asp333, Asp495, and His523 form the catalytic triad of rat soluble epoxide hydrolase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8626766
journal: J Biol Chem
volume: 271
pages: 4223-9
published year: 1996
authors:
  item: Arand M
  item: Wagner H
  item: Oesch F

Primary structure and catalytic mechanism of the epoxide hydrolase from Agrobacterium radiobacter AD1.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9169427
journal: J Biol Chem
volume: 272
pages: 14650-7
published year: 1997
authors:
  item: Rink R
  item: Fennema M
  item: Smids M
  item: Dehmel U
  item: Janssen DB

Mechanism of microsomal epoxide hydrolase. Semifunctional site-specific mutants affecting the alkylation half-reaction.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9485441
journal: Biochemistry
volume: 37
pages: 2897-904
published year: 1998
authors:
  item: Laughlin LT
  item: Tzeng HF
  item: Lin S
  item: Armstrong RN

Semifunctional site-specific mutants affecting the hydrolytic half-reaction of microsomal epoxide hydrolase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9485442
journal: Biochemistry
volume: 37
pages: 2905-11
published year: 1998
authors:
  item: Tzeng HF
  item: Laughlin LT
  item: Armstrong RN

Characterisation of a catabolic epoxide hydrolase from a Corynebacterium sp.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9578475
journal: Eur J Biochem
volume: 253
pages: 173-83
published year: 1998
authors:
  item: Misawa E
  item: Chan Kwo Chion CK
  item: Archer IV
  item: Woodland MP
  item: Zhou NY
  item: Carter SF
  item: Widdowson DA
  item: Leak DJ

Catalytic triad of microsomal epoxide hydrolase: replacement of Glu404 with Asp leads to a strongly increased turnover rate.
type: BibliographicResource
comment: catalysis
references: http://www.ncbi.nlm.nih.gov/pubmed/9854022
journal: Biochem J
volume: 337
pages: 37-43
published year: 1999
authors:
  item: Arand M
  item: Muller F
  item: Mecky A
  item: Hinz W
  item: Urban P
  item: Pompon D
  item: Kellner R
  item: Oesch F

Kinetic mechanism of the enantioselective conversion of styrene oxide by epoxide hydrolase from Agrobacterium radiobacter AD1.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9922181
journal: Biochemistry
volume: 37
pages: 18119-27
published year: 1998
authors:
  item: Rink R
  item: Janssen DB

Epoxide hydrolases and their synthetic applications.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9933984
journal: Adv Biochem Eng Biotechnol
volume: 63
pages: 145-67
published year: 1999
authors:
  item: Orru RV
  item: Archelas A
  item: Furstoss R
  item: Faber K

Kinetic and chemical mechanism of epoxide hydrolase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10065366
journal: Drug Metab Rev
volume: 31
pages: 71-86
published year: 1999
authors:
  item: Armstrong RN

The x-ray structure of epoxide hydrolase from Agrobacterium radiobacter AD1. An enzyme to detoxify harmful epoxides.
type: BibliographicResource
comment: X-ray crystallography (2.1 Angstroms)
references: http://www.ncbi.nlm.nih.gov/pubmed/10329649
journal: J Biol Chem
volume: 274
pages: 14579-86
published year: 1999
authors:
  item: Nardini M
  item: Ridder IS
  item: Rozeboom HJ
  item: Kalk KH
  item: Rink R
  item: Janssen DB
  item: Dijkstra BW
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Detoxification of environmental mutagens and carcinogens: structure, mechanism, and evolution of liver epoxide hydrolase.
type: BibliographicResource
comment: X-ray crystallography (2.8 Angstroms)
references: http://www.ncbi.nlm.nih.gov/pubmed/10485878
journal: Proc Natl Acad Sci U S A
volume: 96
pages: 10637-42
published year: 1999
authors:
  item: Argiriadi MA
  item: Morisseau C
  item: Hammock BD
  item: Christianson DW
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Structure of Aspergillus niger epoxide hydrolase at 1.8 A resolution: implications for the structure and function of the mammalian microsomal class of epoxide hydrolases.
type: BibliographicResource
comment: X-ray crystallography (1.8 Angstroms)
references: http://www.ncbi.nlm.nih.gov/pubmed/10673439
journal: Structure Fold Des
volume: 8
pages: 111-22
published year: 2000
authors:
  item: Zou J
  item: Hallberg BM
  item: Bergfors T
  item: Oesch F
  item: Arand M
  item: Mowbray SL
  item: Jones TA
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Binding of alkylurea inhibitors to epoxide hydrolase implicates active site tyrosines in substrate activation.
type: BibliographicResource
comment: X-ray crystallography
references: http://www.ncbi.nlm.nih.gov/pubmed/10747889
journal: J Biol Chem
volume: 275
pages: 15265-70
published year: 2000
authors:
  item: Argiriadi MA
  item: Morisseau C
  item: Goodrow MH
  item: Dowdy DL
  item: Hammock BD
  item: Christianson DW
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Biochemical evidence for the involvement of tyrosine in epoxide activation during the catalytic cycle of epoxide hydrolase.
type: BibliographicResource
comment: catalysis
references: http://www.ncbi.nlm.nih.gov/pubmed/10806198
journal: J Biol Chem
volume: 275
pages: 23082-8
published year: 2000
authors:
  item: Yamada T
  item: Morisseau C
  item: Maxwell JE
  item: Argiriadi MA
  item: Christianson DW
  item: Hammock BD

Tyrosine residues serve as proton donor in the catalytic mechanism of epoxide hydrolase from Agrobacterium radiobacter.
type: BibliographicResource
comment: catalysis
references: http://www.ncbi.nlm.nih.gov/pubmed/10820034
journal: Biochemistry
volume: 39
pages: 5600-13
published year: 2000
authors:
  item: Rink R
  item: Kingma J
  item: Lutje Spelberg JH
  item: Janssen DB

3-D QSAR analysis of inhibition of murine soluble epoxide hydrolase (MsEH) by benzoylureas, arylureas, and their analogues.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11092551
journal: Bioorg Med Chem
volume: 8
pages: 2663-73
published year: 2000
authors:
  item: Nakagawa Y
  item: Wheelock CE
  item: Morisseau C
  item: Goodrow MH
  item: Hammock BG
  item: Hammock BD

New structural and chemical insight into the catalytic mechanism of epoxide hydrolases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11139132
journal: Drug Metab Rev
volume: 32
pages: 327-38
published year: 2000
authors:
  item: Armstrong RN
  item: Cassidy CS

A theoretical examination of the acid-catalyzed and noncatalyzed ring-opening reaction of an oxirane by nucleophilic addition of acetate. Implications to epoxide hydrolases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11457071
journal: J Am Chem Soc
volume: 123
pages: 3350-7
published year: 2001
authors:
  item: Lau EY
  item: Newby ZE
  item: Bruice TC

Microbial epoxide hydrolases for preparative biotransformations.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11849937
journal: Curr Opin Biotechnol
volume: 12
pages: 552-8
published year: 2001
authors:
  item: Steinreiber A
  item: Faber K

Reaction mechanism of soluble epoxide hydrolase: insights from molecular dynamics simulations.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12465965
journal: J Am Chem Soc
volume: 124
pages: 14558-70
published year: 2002
authors:
  item: Schiott B
  item: Bruice TC

Alpha/Beta-hydrolase fold enzymes: structures, functions and mechanisms.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12369917
journal: Curr Protein Pept Sci
volume: 1
pages: 209-35
published year: 2000
authors:
  item: Holmquist M

Quantitative structure-activity relationships for the enantioselectivity of oxirane ring-opening catalyzed by epoxide hydrolases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12767152
journal: J Chem Inf Comput Sci
volume: 43
pages: 934-40
published year: 2003
authors:
  item: Funar-Timofei S
  item: Suzuki T
  item: Paier JA
  item: Steinreiber A
  item: Faber K
  item: Fabian WM

Polymorphisms in human soluble epoxide hydrolase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12869654
journal: Mol Pharmacol
volume: 64
pages: 482-90
published year: 2003
authors:
  item: Przybyla-Zawislak BD
  item: Srivastava PK
  item: Vazquez-Matias J
  item: Mohrenweiser HW
  item: Maxwell JE
  item: Hammock BD
  item: Bradbury JA
  item: Enayetallah AE
  item: Zeldin DC
  item: Grant DF

Analogue
compound: Epoxide
pdb: 1cr6B02
ligand het code: CPU

Analogue
compound: Epoxide
pdb: 1ek1A02
ligand het code: CIU

Analogue
compound: Epoxide
pdb: 1ek1B02
ligand het code: CIU

Analogue
compound: Epoxide
pdb: 1ek2A02
ligand het code: CDU

Analogue
compound: Epoxide
pdb: 1ek2B02
ligand het code: CDU

ReferenceForCatalyticMechanism
reference index: 2
reference section: Fig.3
reference step: 2

ReferenceForCatalyticMechanism
reference index: 3
reference section: Fig.2, p.4228-4229
reference step: 2

ReferenceForCatalyticMechanism
reference index: 4
reference section: Fig.6, p.14655-14657
reference step: 2

ReferenceForCatalyticMechanism
reference index: 6
reference section: Fig.6, p.2909-2911

ReferenceForCatalyticMechanism
reference index: 9
reference section: Fig.1
reference step: 2

ReferenceForCatalyticMechanism
reference index: 10
reference section: Scheme 6, p.150-152
reference step: 2

ReferenceForCatalyticMechanism
reference index: 11
reference section: Fig.4, p.79-83
reference step: 2

ReferenceForCatalyticMechanism
reference index: 12
reference section: Fig.8, p.14583-14585

ReferenceForCatalyticMechanism
reference index: 13
reference section: Fig.3, p.10638-10639

ReferenceForCatalyticMechanism
reference index: 14
reference section: Fig.4, p.115-116
reference step: 2

ReferenceForCatalyticMechanism
reference index: 15
reference section: p.15269

ReferenceForCatalyticMechanism
reference index: 16
reference section: Fig.1, p.23085-23087
reference step: 2

ReferenceForCatalyticMechanism
reference index: 17
reference section: p.5609-5612

ReferenceForCatalyticMechanism
reference index: 20
reference section: Fig.1, p.332-335

ReferenceForCatalyticMechanism
reference index: 21
reference section: Scheme 1
reference step: 2

ReferenceForCatalyticMechanism
reference index: 22
reference section: Fig.1, p.552-553
reference step: 2

ReferenceForCatalyticMechanism
reference index: 23
reference section: Scheme 2
reference step: 3

ReferenceForCatalyticMechanism
reference index: 24
reference section: Fig.9, p.225-226
reference step: 3