1CR6

CRYSTAL STRUCTURE OF MURINE SOLUBLE EPOXIDE HYDROLASE COMPLEXED WITH CPU INHIBITOR

Summary for 1CR6

• Entry DOI: 10.2210/pdb1cr6/pdb
• Related: 1CQZ
• Descriptor: EPOXIDE HYDROLASE, N-CYCLOHEXYL-N'-(PROPYL)PHENYL UREA (3 entities in total)
• Functional Keywords: homodimer, alpha/beta hydrolase fold, disubstituted urea inhibitor, hydrolase
• Biological source: Mus musculus (house mouse)
• Cellular location: Cytoplasm: P34914
• Total number of polymer chains: 2
• Total formula weight: 125684.83

Authors

Argiriadi, M.A.,Morisseau, C.,Hammock, B.D.,Christianson, D.W. (deposition date: 1999-08-13, release date: 1999-11-19, Last modification date: 2024-02-07)

Primary citation

Argiriadi, M.A.,Morisseau, C.,Hammock, B.D.,Christianson, D.W.
Detoxification of environmental mutagens and carcinogens: structure, mechanism, and evolution of liver epoxide hydrolase.
Proc.Natl.Acad.Sci.USA, 96:10637-10642, 1999

PubMed Abstract: 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.

PubMed: 10485878
DOI: 10.1073/pnas.96.19.10637

Experimental method

X-RAY DIFFRACTION (2.8 Å)