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5e58

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Crystal Structure Of Cytochrome P450 2B35 from Desert Woodrat Neotoma Lepida in complex with 4-(4-chlorophenyl)imidazole

Structural highlights

5e58 is a 6 chain structure with sequence from Neotoma lepida. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:	, , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

J9JD66_NEOLE

Publication Abstract from PubMed

Crystal structures of CYP2B35 and CYP2B37 from the desert woodrat were solved in complex with 4-(4-chlorophenyl) imidazole (4-CPI). The closed conformation of CYP2B35 contained two molecules of 4-CPI within the active site, whereas the CYP2B37 structure demonstrated an open conformation with three 4-CPI molecules, one within the active site and the other two in the substrate access channel. To probe structure-function relationships of CYP2B35, CYP2B37, and the related CYP2B36 we tested the O-dealkylation of three series of related substrates, namely 7-alkoxycoumarins, 7-alkoxy-4-(trifluoromethyl)coumarins, and 7-alkoxy-4-methylcoumarins with a C1-C7 side chain. CYP2B35 showed the highest catalytic efficiency (kcat/KM) with 7-heptoxycoumarin as a substrate, followed by 7-hexoxycoumarin. In contrast, CYP2B37 showed the highest catalytic efficiency with 7-ethoxy-4-(trifluoromethyl)coumarin (7-EFC), followed by 7-methoxy-4-(trifluoromethyl)coumarin (7-MFC). CYP2B35 had no dealkylation activity with 7-MFC or 7-EFC. Furthermore, the new CYP2B-4-CPI bound structures were used as templates for docking the 7-substituted coumarin derivatives, which revealed orientations consistent with the functional studies. In addition, the observation of multiple -Cl and -NH-pi interactions of 4-CPI with the aromatic side chains in the CYP2B35 and CYP2B37 structures provide insight into the influence of such functional groups on CYP2B-ligand binding affinity and specificity. To conclude, structural, computational, and functional analysis revealed striking differences between the active sites of CYP2B35 and CYP2B37 that will aid in the elucidation of new structure-activity relationships.

Structure-Function Analysis of Mammalian CYP2B Enzymes using 7-Substituted Coumarin Derivatives as Probes: Utility of Crystal Structures and Molecular Modeling in Understanding Xenobiotic Metabolism.,Shah MB, Liu J, Huo L, Zhang Q, Dearing MD, Wilderman PR, Szklarz GD, Stout CD, Halpert JR Mol Pharmacol. 2016 Jan 29. pii: mol.115.102111. PMID:26826176^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Shah MB, Liu J, Huo L, Zhang Q, Dearing MD, Wilderman PR, Szklarz GD, Stout CD, Halpert JR. Structure-Function Analysis of Mammalian CYP2B Enzymes using 7-Substituted Coumarin Derivatives as Probes: Utility of Crystal Structures and Molecular Modeling in Understanding Xenobiotic Metabolism. Mol Pharmacol. 2016 Jan 29. pii: mol.115.102111. PMID:26826176 doi:http://dx.doi.org/10.1124/mol.115.102111

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5e58"

Categories: Large Structures | Neotoma lepida | Halpert JR | Shah MB | Stout CD

@@ Line 3: / Line 3: @@
 <StructureSection load='5e58' size='340' side='right'caption='[[5e58]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5e58]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Desert_woodrat Desert woodrat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E58 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E58 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5e58]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Neotoma_lepida Neotoma lepida]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E58 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5E58 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CM5:5-CYCLOHEXYL-1-PENTYL-BETA-D-MALTOSIDE'>CM5</scene>, <scene name='pdbligand=CPZ:4-(4-CHLOROPHENYL)IMIDAZOLE'>CPZ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=SUC:SUCROSE'>SUC</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP2B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=56216 Desert woodrat])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CM5:5-CYCLOHEXYL-1-PENTYL-BETA-D-MALTOSIDE'>CM5</scene>, <scene name='pdbligand=CPZ:4-(4-CHLOROPHENYL)IMIDAZOLE'>CPZ</scene>, <scene name='pdbligand=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PRD_900003:sucrose'>PRD_900003</scene></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=5e58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e58 OCA], [http://pdbe.org/5e58 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e58 RCSB], [http://www.ebi.ac.uk/pdbsum/5e58 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e58 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5e58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e58 OCA], [https://pdbe.org/5e58 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5e58 RCSB], [https://www.ebi.ac.uk/pdbsum/5e58 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5e58 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/J9JD66_NEOLE J9JD66_NEOLE]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Desert woodrat]]
 [[Category: Large Structures]]
-[[Category: Halpert, J R]]
-[[Category: Shah, M B]]
-[[Category: Stout, C D]]
-[[Category: Cyp2b35]]
-[[Category: Cytochrome p450]]
 [[Category: Neotoma lepida]]
-[[Category: Oxidoreductase]]
+[[Category: Halpert JR]]
-[[Category: Woodrat]]
+[[Category: Shah MB]]
+[[Category: Stout CD]]

5e58

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Current revision

Crystal Structure Of Cytochrome P450 2B35 from Desert Woodrat Neotoma Lepida in complex with 4-(4-chlorophenyl)imidazole

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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