5uda: Difference between revisions
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==Crystal structure of CYP2B6 (Y226H/K262R) in complex with a monoterpene bornane== | |||
<StructureSection load='5uda' size='340' side='right' caption='[[5uda]], [[Resolution|resolution]] 1.93Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5uda]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UDA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UDA FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAE:CAMPHANE'>CAE</scene>, <scene name='pdbligand=CM5:5-CYCLOHEXYL-1-PENTYL-BETA-D-MALTOSIDE'>CM5</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5uec|5uec]]</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5uda FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uda OCA], [http://pdbe.org/5uda PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uda RCSB], [http://www.ebi.ac.uk/pdbsum/5uda PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uda ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/CP2B6_HUMAN CP2B6_HUMAN]] Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.<ref>PMID:11695850</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Numerous cytochrome P450 (CYP) 2B6 substrates including drugs and environmental chemicals are halogenated. To assess the role of halogen-pi bonds in substrate selectivity and orientation in the active site, structures of four CYP2B6 monoterpenoid complexes were solved by X-ray crystallography. Bornyl bromide exhibited dual orientations in the active site with the predominant orientation revealing a bromine-pi bond with the Phe108 side chain. Bornane demonstrated two orientations with equal occupancy; in both, the C2 atom that bears the bromine in bornyl bromide was displaced by more than 2.5 A compared with the latter complex. The bromine in myrtenyl bromide pi-bonded with Phe297 in CYP2B6, whereas the two major orientations in the active site mutant I114V exhibited bromine-pi interactions with two additional residues, Phe108 and Phe115. Analysis of existing structures suggests that halogen-pi interactions may be unique to the CYP2B enzymes within CYP family 2 but are also important for CYP3A enzymes. | |||
Halogen-pi Interactions in the Cytochrome P450 Active Site: Structural Insights into Human CYP2B6 Substrate Selectivity.,Shah MB, Liu J, Zhang Q, Stout CD, Halpert JR ACS Chem Biol. 2017 Apr 6. doi: 10.1021/acschembio.7b00056. PMID:28368100<ref>PMID:28368100</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Shah, M | <div class="pdbe-citations 5uda" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Halpert, J R]] | |||
[[Category: Shah, M B]] | |||
[[Category: Cyp2b6]] | |||
[[Category: Cytochrome p450]] | |||
[[Category: Oxidoreductase]] | |||
Revision as of 14:35, 12 April 2017
Crystal structure of CYP2B6 (Y226H/K262R) in complex with a monoterpene bornaneCrystal structure of CYP2B6 (Y226H/K262R) in complex with a monoterpene bornane
Structural highlights
Function[CP2B6_HUMAN] Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.[1] Publication Abstract from PubMedNumerous cytochrome P450 (CYP) 2B6 substrates including drugs and environmental chemicals are halogenated. To assess the role of halogen-pi bonds in substrate selectivity and orientation in the active site, structures of four CYP2B6 monoterpenoid complexes were solved by X-ray crystallography. Bornyl bromide exhibited dual orientations in the active site with the predominant orientation revealing a bromine-pi bond with the Phe108 side chain. Bornane demonstrated two orientations with equal occupancy; in both, the C2 atom that bears the bromine in bornyl bromide was displaced by more than 2.5 A compared with the latter complex. The bromine in myrtenyl bromide pi-bonded with Phe297 in CYP2B6, whereas the two major orientations in the active site mutant I114V exhibited bromine-pi interactions with two additional residues, Phe108 and Phe115. Analysis of existing structures suggests that halogen-pi interactions may be unique to the CYP2B enzymes within CYP family 2 but are also important for CYP3A enzymes. Halogen-pi Interactions in the Cytochrome P450 Active Site: Structural Insights into Human CYP2B6 Substrate Selectivity.,Shah MB, Liu J, Zhang Q, Stout CD, Halpert JR ACS Chem Biol. 2017 Apr 6. doi: 10.1021/acschembio.7b00056. PMID:28368100[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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