4c4x: Difference between revisions
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==Crystal structure of human bifunctional epoxide hydroxylase 2 complexed with C9== | ==Crystal structure of human bifunctional epoxide hydroxylase 2 complexed with C9== | ||
<StructureSection load='4c4x' size='340' side='right' caption='[[4c4x]], [[Resolution|resolution]] 2.17Å' scene=''> | <StructureSection load='4c4x' size='340' side='right'caption='[[4c4x]], [[Resolution|resolution]] 2.17Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4c4x]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C4X OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4c4x]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C4X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C4X FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.17Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=W9M:3-(3,4-DICHLOROPHENYL)-1,1-DIMETHYL-UREA'>W9M</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4c4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c4x OCA], [https://pdbe.org/4c4x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c4x RCSB], [https://www.ebi.ac.uk/pdbsum/4c4x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c4x ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/HYES_HUMAN HYES_HUMAN] Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides. Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid, 12-phosphonooxy-octadec-9E-enoic acid, and p-nitrophenyl phospate.<ref>PMID:12574508</ref> <ref>PMID:12574510</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 21: | Line 21: | ||
==See Also== | ==See Also== | ||
*[[Epoxide hydrolase|Epoxide hydrolase]] | *[[Epoxide hydrolase 3D structures|Epoxide hydrolase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Becker | [[Category: Homo sapiens]] | ||
[[Category: Elshorst | [[Category: Large Structures]] | ||
[[Category: Griesinger | [[Category: Becker S]] | ||
[[Category: Hessler | [[Category: Elshorst B]] | ||
[[Category: Krimm | [[Category: Griesinger C]] | ||
[[Category: Langer | [[Category: Hessler G]] | ||
[[Category: Lee | [[Category: Krimm I]] | ||
[[Category: Mazur | [[Category: Langer T]] | ||
[[Category: Monecke | [[Category: Lee D]] | ||
[[Category: Pilger | [[Category: Mazur A]] | ||
[[Category: Schiffer | [[Category: Monecke P]] | ||
[[Category: Schreuder | [[Category: Pilger J]] | ||
[[Category: Wegstroth | [[Category: Schiffer A]] | ||
[[Category: Wendt | [[Category: Schreuder H]] | ||
[[Category: Wegstroth M]] | |||
[[Category: Wendt K-U]] | |||
Latest revision as of 15:03, 20 December 2023
Crystal structure of human bifunctional epoxide hydroxylase 2 complexed with C9Crystal structure of human bifunctional epoxide hydroxylase 2 complexed with C9
Structural highlights
FunctionHYES_HUMAN Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides. Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid, 12-phosphonooxy-octadec-9E-enoic acid, and p-nitrophenyl phospate.[1] [2] Publication Abstract from PubMedStructure-based drug design (SBDD) is a powerful and widely used approach to optimize affinity of drug candidates. With the recently introduced INPHARMA method, the binding mode of small molecules to their protein target can be characterized even if no spectroscopic information about the protein is known. Here, we show that the combination of the spin-diffusion-based NMR methods INPHARMA, trNOE, and STD results in an accurate scoring function for docking modes and therefore determination of protein-ligand complex structures. Applications are shown on the model system protein kinase A and the drug targets glycogen phosphorylase and soluble epoxide hydrolase (sEH). Multiplexing of several ligands improves the reliability of the scoring function further. The new score allows in the case of sEH detecting two binding modes of the ligand in its binding site, which was corroborated by X-ray analysis. A Combination of Spin Diffusion Methods for the Determination of Protein-Ligand Complex Structural Ensembles.,Pilger J, Mazur A, Monecke P, Schreuder H, Elshorst B, Bartoschek S, Langer T, Schiffer A, Krimm I, Wegstroth M, Lee D, Hessler G, Wendt KU, Becker S, Griesinger C Angew Chem Int Ed Engl. 2015 Apr 15. doi: 10.1002/anie.201500671. PMID:25877959[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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