1cr6
CRYSTAL STRUCTURE OF MURINE SOLUBLE EPOXIDE HYDROLASE COMPLEXED WITH CPU INHIBITOR
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| , resolution 2.8Å | |||||||
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| Ligands: | |||||||
| Activity: | Microsomal epoxide hydrolase, with EC number 3.3.2.9 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
OverviewOverview
The crystal structure of recombinant murine liver cytosolic epoxide hydrolase (EC 3.3.2.3) has been determined at 2.8-A resolution. The binding of a nanomolar affinity inhibitor confirms the active site location in the C-terminal domain; this domain is similar to that of haloalkane dehalogenase and shares the alpha/beta hydrolase fold. A structure-based mechanism is proposed that illuminates the unique chemical strategy for the activation of endogenous and man-made epoxide substrates for hydrolysis and detoxification. Surprisingly, a vestigial active site is found in the N-terminal domain similar to that of another enzyme of halocarbon metabolism, haloacid dehalogenase. Although the vestigial active site does not participate in epoxide hydrolysis, the vestigial domain plays a critical structural role by stabilizing the dimer in a distinctive domain-swapped architecture. Given the genetic and structural relationships among these enzymes of xenobiotic metabolism, a structure-based evolutionary sequence is postulated.
About this StructureAbout this Structure
1CR6 is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
Detoxification of environmental mutagens and carcinogens: structure, mechanism, and evolution of liver epoxide hydrolase., Argiriadi MA, Morisseau C, Hammock BD, Christianson DW, Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10637-42. PMID:10485878
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