Epoxide hydrolase

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microsomal epoxide hydrolase
Identifiers
EC number 3.3.2.9
CAS number 9048-63-9
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
soluble epoxide hydrolase
Epoxide Hydrolase B (2E3J).png
Epoxide hydrolase from Mycobacterium tuberculosis.[1]
Identifiers
EC number 3.3.2.10
CAS number 9048-63-9
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

Epoxide hydrolase (also known as epoxide hydratase) functions in detoxification during drug metabolism. It converts epoxides to trans-dihydrodiols, which can be conjugated and excreted from the body. Epoxides result from the degradation of aromatic compounds. Deficiency in this enzyme in patients receiving aromatic-type anti-epileptic drugs such as phenytoin is reported to lead to DRESS syndrome.

Epoxides are significant as cytochrome P450 oxidase metabolites of unsaturated carbon-carbon bonds, but are also mutagenic. Epoxide hydrolase is present in large quantity on endoplasmic reticulum.

Drug target[edit]

Mycobacterium tuberculosis, the major causative agent of tuberculosis, expresses at least six different forms of epoxide hydrolase (forms A-F). The structure of epoxide hydrolase B reveals that the enzyme is a monomer and contains an alpha/beta hydrolase fold. In addition to providing insights into the enzyme mechanism, this hydrolase currently serves as a platform for rational drug design of potent inhibitors. In particular, urea based inhibitors have been developed. These inhibitors directly target the catalytic cavity. It is hypothesized that the structure of epoxide hydrolase B may allow for drug design to inhibit all other Mycobacterium tuberculosis hydrolases as long as they contain similar alpha/beta folds.

The structure of hydrolase B contains a cap domain, which is hypothesized to regulate the active site of the hydrolase.[1] Furthermore, Asp104, His333, and Asp302 form the catalytic triad of the protein and is critical to function of the protein.

At present, other structures of Mycobacterium tuberculosis hydrolase have not been solved.

Isozymes[edit]

Humans express the following four isozymes of epoxide hydrolase:

epoxide hydrolase 1, microsomal
Identifiers
Symbol EPHX1
Entrez 2052
HUGO 3401
OMIM 132810
RefSeq NM_000120
UniProt Q9NQV0
Other data
Locus Chr. 1 q42.1
epoxide hydrolase 2, cytoplasmic
Identifiers
Symbol EPHX2
Entrez 2053
HUGO 3402
OMIM 132811
RefSeq NM_001979
UniProt P34913
Other data
Locus Chr. 8 p21
epoxide hydrolase 3
Identifiers
Symbol EPHX3
Alt. symbols ABHD9
Entrez 79852
HUGO 23760
RefSeq NM_024794
UniProt Q9H6B9
Other data
Locus Chr. 19 p13.13
epoxide hydrolase 4
Identifiers
Symbol EPHX4
Alt. symbols ABHD7
Entrez 253152
HUGO 23758
RefSeq NM_173567
UniProt Q8IUS5
Other data
Locus Chr. 1 p22.1

References[edit]

  1. ^ a b PDB 2E3J; Biswal BK, Morisseau C, Garen G, Cherney MM, Garen C, Niu C, Hammock BD, James MN. (September 2008). "The molecular structure of epoxide hydrolase B from Mycobacterium tuberculosis and its complex with a urea-based inhibitor.". J. Mol. Bio. 381 (4): 897–912. doi:10.1016/j.jmb.2008.06.030. PMID 18585390. ; rendered via PyMOL

External links[edit]