1cr6
From Proteopedia
(New page: 200px<br /><applet load="1cr6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1cr6, resolution 2.8Å" /> '''CRYSTAL STRUCTURE OF ...) |
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| - | [[Image:1cr6.gif|left|200px]]<br /><applet load="1cr6" size=" | + | [[Image:1cr6.gif|left|200px]]<br /><applet load="1cr6" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1cr6, resolution 2.8Å" /> | caption="1cr6, resolution 2.8Å" /> | ||
'''CRYSTAL STRUCTURE OF MURINE SOLUBLE EPOXIDE HYDROLASE COMPLEXED WITH CPU INHIBITOR'''<br /> | '''CRYSTAL STRUCTURE OF MURINE SOLUBLE EPOXIDE HYDROLASE COMPLEXED WITH CPU INHIBITOR'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structure of recombinant murine liver cytosolic epoxide | + | 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 Structure== | ==About this Structure== | ||
| - | 1CR6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with CPU as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Microsomal_epoxide_hydrolase Microsomal epoxide hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.9 3.3.2.9] Full crystallographic information is available from [http:// | + | 1CR6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=CPU:'>CPU</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Microsomal_epoxide_hydrolase Microsomal epoxide hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.9 3.3.2.9] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CR6 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Argiriadi, M | + | [[Category: Argiriadi, M A.]] |
| - | [[Category: Christianson, D | + | [[Category: Christianson, D W.]] |
| - | [[Category: Hammock, B | + | [[Category: Hammock, B D.]] |
[[Category: Morisseau, C.]] | [[Category: Morisseau, C.]] | ||
[[Category: CPU]] | [[Category: CPU]] | ||
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[[Category: homodimer]] | [[Category: homodimer]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:08:55 2008'' |
Revision as of 10:08, 21 February 2008
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CRYSTAL STRUCTURE OF MURINE SOLUBLE EPOXIDE HYDROLASE COMPLEXED WITH CPU INHIBITOR
Overview
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 Structure
1CR6 is a Single protein structure of sequence from Mus musculus with as ligand. Active as Microsomal epoxide hydrolase, with EC number 3.3.2.9 Full crystallographic information is available from OCA.
Reference
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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