3tk3 - Revision history

OCA at 10:19, 13 August 2026

2026-08-13T10:19:54Z

← Older revision		Revision as of 10:19, 13 August 2026
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	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/CP2B4_RABIT CP2B4_RABIT] 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. In the epoxidation of arachidonic acid it has a unique preference for the 5,6-olefin.		[https://www.uniprot.org/uniprot/CP2B4_RABIT CP2B4_RABIT] 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. In the epoxidation of arachidonic acid it has a unique preference for the 5,6-olefin.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Residues located outside of the active site of cytochromes P450 2B have exhibited importance in ligand binding, structural stability, and drug metabolism. However, contributions of non-active site residues to the plasticity of these enzymes are not known. Thus, a systematic investigation was undertaken of unique residue-residue interactions found in crystal structures of P450 2B4 in complex with 4-(4-chlorophenyl)imidazole (4-CPI), a closed conformation, or in complex with bifonazole, an expanded conformation. Nineteen mutants distributed over eleven sites were constructed, expressed in E. coli, and purified. Most mutants showed significantly decreased expression, especially in the case of interactions found in the 4-CPI structure. Six mutants (H172A, H172F, H172Q, L437A, E474D, and E474Q) were chosen for detailed functional analysis. Among these, the K(s) of H172F for bifonazole was approximately 20-times higher than wild type 2B4, and the K(s) of L437A for 4-CPI was approximately 50-times higher than wild type, leading to significantly altered inhibitor selectivity. Enzyme function was tested with the substrates 7-ethoxy-4-(trifluoromethyl)coumarin (7-EFC), 7-methoxy-4-(trifluoromethyl)coumarin (7-MFC), and 7-benzyloxyresorufin (7-BR). H172F was inactive with all three substrates, and L437A did not turn over 7-BR. Furthermore, H172A, H172Q, E474D and E474Q showed large changes in k(cat) /K(M) for each of the three substrates, in some cases up to 50-fold. Concurrent molecular dynamics simulations yield distances between some of the residues in these putative interaction pairs that are not consistent with contact. The results indicate that small changes in the protein scaffold lead to large differences in solution behavior and enzyme function.

			Investigation by site-directed mutagenesis of the role of cytochrome P450 2B4 non-active site residues in protein-ligand interactions based on crystal structures of the ligand-bound enzyme.,Wilderman PR, Gay SC, Jang HH, Zhang Q, Stout CD, Halpert JR FEBS J. 2011 Nov 3. doi: 10.1111/j.1742-4658.2011.08411.x. PMID:22051155<ref>PMID:22051155</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 3tk3" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Cytochrome P450 3D structures\|Cytochrome P450 3D structures]]		*[[Cytochrome P450 3D structures\|Cytochrome P450 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 13:31, 14 March 2024

2024-03-14T13:31:33Z

← Older revision		Revision as of 13:31, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3tk3' size='340' side='right'caption='[[3tk3]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='3tk3' size='340' side='right'caption='[[3tk3]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3tk3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~European_rabbit European rabbit~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TK3 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3tk3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TK3 FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=CPZ:4-(4~~-~~CHLOROPHENYL)IMIDAZOLE'>CPZ</scene>~~, ~~<scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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]] 2.8001Å</td></tr>
	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>CYP2B4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9986 European rabbit])</td~~><~~/tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CPZ:4-(4-CHLOROPHENYL)IMIDAZOLE'>CPZ</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>~~[https://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1]~~ </~~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=3tk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tk3 OCA], [https://pdbe.org/3tk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tk3 RCSB], [https://www.ebi.ac.uk/pdbsum/3tk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tk3 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=3tk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tk3 OCA], [https://pdbe.org/3tk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tk3 RCSB], [https://www.ebi.ac.uk/pdbsum/3tk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tk3 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/CP2B4_RABIT CP2B4_RABIT]] 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. In the epoxidation of arachidonic acid it has a unique preference for the 5,6-olefin.		[https://www.uniprot.org/uniprot/CP2B4_RABIT CP2B4_RABIT] 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. In the epoxidation of arachidonic acid it has a unique preference for the 5,6-olefin.
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Residues located outside of the active site of cytochromes P450 2B have exhibited importance in ligand binding, structural stability, and drug metabolism. However, contributions of non-active site residues to the plasticity of these enzymes are not known. Thus, a systematic investigation was undertaken of unique residue-residue interactions found in crystal structures of P450 2B4 in complex with 4-(4-chlorophenyl)imidazole (4-CPI), a closed conformation, or in complex with bifonazole, an expanded conformation. Nineteen mutants distributed over eleven sites were constructed, expressed in E. coli, and purified. Most mutants showed significantly decreased expression, especially in the case of interactions found in the 4-CPI structure. Six mutants (H172A, H172F, H172Q, L437A, E474D, and E474Q) were chosen for detailed functional analysis. Among these, the K(s) of H172F for bifonazole was approximately 20-times higher than wild type 2B4, and the K(s) of L437A for 4-CPI was approximately 50-times higher than wild type, leading to significantly altered inhibitor selectivity. Enzyme function was tested with the substrates 7-ethoxy-4-(trifluoromethyl)coumarin (7-EFC), 7-methoxy-4-(trifluoromethyl)coumarin (7-MFC), and 7-benzyloxyresorufin (7-BR). H172F was inactive with all three substrates, and L437A did not turn over 7-BR. Furthermore, H172A, H172Q, E474D and E474Q showed large changes in k(cat) /K(M) for each of the three substrates, in some cases up to 50-fold. Concurrent molecular dynamics simulations yield distances between some of the residues in these putative interaction pairs that are not consistent with contact. The results indicate that small changes in the protein scaffold lead to large differences in solution behavior and enzyme function.

	Investigation by site-directed mutagenesis of the role of cytochrome P450 2B4 non-active site residues in protein-ligand interactions based on crystal structures of the ligand-bound enzyme.,Wilderman PR, Gay SC, Jang HH, Zhang Q, Stout CD, Halpert JR FEBS J. 2011 Nov 3. doi: 10.1111/j.1742-4658.2011.08411.x. PMID:22051155<ref>PMID:22051155</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 3tk3" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==
	*[[Cytochrome P450 3D structures\|Cytochrome P450 3D structures]]		*[[Cytochrome P450 3D structures\|Cytochrome P450 3D structures]]
	~~== References ==~~
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	~~[[Category: European rabbit]]~~
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: ~~Unspecific monooxygenase~~]]		[[Category: Oryctolagus cuniculus]]
	[[Category: Gay~~, S C~~]]		[[Category: Gay SC]]
	[[Category: Halpert~~, J R~~]]		[[Category: Halpert JR]]
	[[Category: Jang~~, H H~~]]		[[Category: Jang HH]]
	[[Category: Stout~~, C D~~]]		[[Category: Stout CD]]
	[[Category: Wilderman~~, P R~~]]		[[Category: Wilderman PR]]
	[[Category: Zhang, Q]]		[[Category: Zhang Q]]
	~~[[Category: Cyp 2b4]]~~
	~~[[Category: Cyp lm2]]~~
	~~[[Category: Cytochrome p450 2b4]]~~
	~~[[Category: Membrane protein]]~~
	~~[[Category: Monooxygenase]]~~
	~~[[Category: Oxidoreductase]]~~
	~~[[Category: P450~~]]

OCA at 17:01, 6 July 2022

2022-07-06T17:01:44Z

← Older revision		Revision as of 17:01, 6 July 2022
Line 1:		Line 1:

	==Cytochrome P450 2B4 mutant L437A in complex with 4-(4-chlorophenyl)imidazole==		==Cytochrome P450 2B4 mutant L437A in complex with 4-(4-chlorophenyl)imidazole==
	<StructureSection load='3tk3' size='340' side='right' caption='[[3tk3]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='3tk3' size='340' side='right'caption='[[3tk3]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3tk3]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/European_rabbit European rabbit]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TK3 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3TK3 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3tk3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/European_rabbit European rabbit]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TK3 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CPZ:4-(4-CHLOROPHENYL)IMIDAZOLE'>CPZ</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CPZ:4-(4-CHLOROPHENYL)IMIDAZOLE'>CPZ</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP2B4 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 European rabbit])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP2B4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 European rabbit])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] </span></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=3tk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tk3 OCA], [~~http~~://pdbe.org/3tk3 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3tk3 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3tk3 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3tk3 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=3tk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tk3 OCA], [https://pdbe.org/3tk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tk3 RCSB], [https://www.ebi.ac.uk/pdbsum/3tk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tk3 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/CP2B4_RABIT CP2B4_RABIT]] 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. In the epoxidation of arachidonic acid it has a unique preference for the 5,6-olefin.		[[https://www.uniprot.org/uniprot/CP2B4_RABIT CP2B4_RABIT]] 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. In the epoxidation of arachidonic acid it has a unique preference for the 5,6-olefin.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 22:

	==See Also==		==See Also==
	*[[Cytochrome P450\|Cytochrome P450]]		*[[Cytochrome P450 3D structures\|Cytochrome P450 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 28:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: European rabbit]]		[[Category: European rabbit]]
			[[Category: Large Structures]]
	[[Category: Unspecific monooxygenase]]		[[Category: Unspecific monooxygenase]]
	[[Category: Gay, S C]]		[[Category: Gay, S C]]

OCA at 07:45, 5 August 2016

2016-08-05T07:45:46Z

← Older revision		Revision as of 07:45, 5 August 2016
Line 1:		Line 1:

	==Cytochrome P450 2B4 mutant L437A in complex with 4-(4-chlorophenyl)imidazole==		==Cytochrome P450 2B4 mutant L437A in complex with 4-(4-chlorophenyl)imidazole==
	<StructureSection load='3tk3' size='340' side='right' caption='[[3tk3]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='3tk3' size='340' side='right' caption='[[3tk3]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3tk3]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Oryctolagus_cuniculus Oryctolagus cuniculus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TK3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TK3 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3tk3]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/European_rabbit European rabbit]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TK3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TK3 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CPZ:4-(4-CHLOROPHENYL)IMIDAZOLE'>CPZ</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CPZ:4-(4-CHLOROPHENYL)IMIDAZOLE'>CPZ</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP2B4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 ~~Oryctolagus cuniculus~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP2B4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 European rabbit])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] </span></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=3tk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tk3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tk3 RCSB], [http://www.ebi.ac.uk/pdbsum/3tk3 PDBsum]</span></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=3tk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tk3 OCA], [http://pdbe.org/3tk3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tk3 RCSB], [http://www.ebi.ac.uk/pdbsum/3tk3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tk3 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 3tk3" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Oryctolagus cuniculus~~]]		[[Category: European rabbit]]
	[[Category: Unspecific monooxygenase]]		[[Category: Unspecific monooxygenase]]
	[[Category: Gay, S C]]		[[Category: Gay, S C]]

OCA at 17:00, 25 December 2014

2014-12-25T17:00:34Z

← Older revision		Revision as of 17:00, 25 December 2014
Line 8:		Line 8:
	<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=3tk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tk3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tk3 RCSB], [http://www.ebi.ac.uk/pdbsum/3tk3 PDBsum]</span></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=3tk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tk3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tk3 RCSB], [http://www.ebi.ac.uk/pdbsum/3tk3 PDBsum]</span></td></tr>
	</table>		</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/CP2B4_RABIT CP2B4_RABIT]] 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. In the epoxidation of arachidonic acid it has a unique preference for the 5,6-olefin.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 17:48, 9 December 2014

2014-12-09T17:48:27Z

← Older revision		Revision as of 17:48, 9 December 2014
Line 1:		Line 1:
	[[~~Image~~:~~3tk3~~.~~png~~\|~~left~~\|~~200px~~]]		==Cytochrome P450 2B4 mutant L437A in complex with 4-(4-chlorophenyl)imidazole==
			<StructureSection load='3tk3' size='340' side='right' caption='[[3tk3]], [[Resolution\|resolution]] 2.80Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[3tk3]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TK3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TK3 FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CPZ:4-(4-CHLOROPHENYL)IMIDAZOLE'>CPZ</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP2B4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 Oryctolagus cuniculus])</td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] </span></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=3tk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tk3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tk3 RCSB], [http://www.ebi.ac.uk/pdbsum/3tk3 PDBsum]</span></td></tr>
			</table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Residues located outside of the active site of cytochromes P450 2B have exhibited importance in ligand binding, structural stability, and drug metabolism. However, contributions of non-active site residues to the plasticity of these enzymes are not known. Thus, a systematic investigation was undertaken of unique residue-residue interactions found in crystal structures of P450 2B4 in complex with 4-(4-chlorophenyl)imidazole (4-CPI), a closed conformation, or in complex with bifonazole, an expanded conformation. Nineteen mutants distributed over eleven sites were constructed, expressed in E. coli, and purified. Most mutants showed significantly decreased expression, especially in the case of interactions found in the 4-CPI structure. Six mutants (H172A, H172F, H172Q, L437A, E474D, and E474Q) were chosen for detailed functional analysis. Among these, the K(s) of H172F for bifonazole was approximately 20-times higher than wild type 2B4, and the K(s) of L437A for 4-CPI was approximately 50-times higher than wild type, leading to significantly altered inhibitor selectivity. Enzyme function was tested with the substrates 7-ethoxy-4-(trifluoromethyl)coumarin (7-EFC), 7-methoxy-4-(trifluoromethyl)coumarin (7-MFC), and 7-benzyloxyresorufin (7-BR). H172F was inactive with all three substrates, and L437A did not turn over 7-BR. Furthermore, H172A, H172Q, E474D and E474Q showed large changes in k(cat) /K(M) for each of the three substrates, in some cases up to 50-fold. Concurrent molecular dynamics simulations yield distances between some of the residues in these putative interaction pairs that are not consistent with contact. The results indicate that small changes in the protein scaffold lead to large differences in solution behavior and enzyme function.

	~~{{STRUCTURE_3tk3\| PDB=3tk3 \| SCENE= }}~~		Investigation by site-directed mutagenesis of the role of cytochrome P450 2B4 non-active site residues in protein-ligand interactions based on crystal structures of the ligand-bound enzyme.,Wilderman PR, Gay SC, Jang HH, Zhang Q, Stout CD, Halpert JR FEBS J. 2011 Nov 3. doi: 10.1111/j.1742-4658.2011.08411.x. PMID:22051155<ref>PMID:22051155</ref>

	~~===Cytochrome P450 2B4 mutant L437A in complex with 4-(4-chlorophenyl)imidazole===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
	~~{{ABSTRACT_PUBMED_22051155}}~~

	~~==About this Structure==~~
	~~[[3tk3]] is~~ a ~~4 chain structure with sequence from [http://en.wikipedia~~.~~org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]~~. ~~Full crystallographic information is available from [http://oca~~.~~weizmann.ac.il/oca-bin~~/~~ocashort?id=3TK3 OCA].~~

	==See Also==		==See Also==
	*[[Cytochrome P450\|Cytochrome P450]]		*[[Cytochrome P450\|Cytochrome P450]]
			== References ==
	==~~Reference~~==		<references/>
	<~~ref group="xtra">PMID:022051155<~~/~~ref~~><ref group="xtra">PMID:016373351</ref><ref group="xtra">PMID:015100217</ref><ref group="xtra">PMID:014563924</ref><ref group="xtra">PMID:017887776</ref><ref group="xtra">PMID:019397311</ref><ref group="xtra">PMID:020815363</ref><ref group="xtra">PMID:020880847</ref><ref group="xtra">PMID:021510666</ref><references group="xtra"/>		__TOC__
			</StructureSection>
	[[Category: Oryctolagus cuniculus]]		[[Category: Oryctolagus cuniculus]]
	[[Category: Unspecific monooxygenase]]		[[Category: Unspecific monooxygenase]]
	[[Category: Gay, S C.]]		[[Category: Gay, S C]]
	[[Category: Halpert, J R.]]		[[Category: Halpert, J R]]
	[[Category: Jang, H H.]]		[[Category: Jang, H H]]
	[[Category: Stout, C D.]]		[[Category: Stout, C D]]
	[[Category: Wilderman, P R.]]		[[Category: Wilderman, P R]]
	[[Category: Zhang, Q.]]		[[Category: Zhang, Q]]
	[[Category: Cyp 2b4]]		[[Category: Cyp 2b4]]
	[[Category: Cyp lm2]]		[[Category: Cyp lm2]]

OCA at 19:12, 20 October 2012

2012-10-20T19:12:19Z

← Older revision		Revision as of 19:12, 20 October 2012
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	==About this Structure==		==About this Structure==
	[[3tk3]] is a 4 chain structure ~~of [[Cytochrome P450]]~~ with sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TK3 OCA].		[[3tk3]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TK3 OCA].

	==See Also==		==See Also==

OCA at 06:36, 27 July 2012

2012-07-27T06:36:34Z

← Older revision		Revision as of 06:36, 27 July 2012
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	[[Image:3tk3.png\|left\|200px]]		[[Image:3tk3.png\|left\|200px]]

	~~<!--~~
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	{{STRUCTURE_3tk3\| PDB=3tk3 \| SCENE= }}		{{STRUCTURE_3tk3\| PDB=3tk3 \| SCENE= }}

	===Cytochrome P450 2B4 mutant L437A in complex with 4-(4-chlorophenyl)imidazole===		===Cytochrome P450 2B4 mutant L437A in complex with 4-(4-chlorophenyl)imidazole===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_22051155}}, adds the Publication Abstract to the page~~
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	{{ABSTRACT_PUBMED_22051155}}		{{ABSTRACT_PUBMED_22051155}}

	==About this Structure==		==About this Structure==
	[[3tk3]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TK3 OCA].		[[3tk3]] is a 4 chain structure of [[Cytochrome P450]] with sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TK3 OCA].

			==See Also==
			*[[Cytochrome P450\|Cytochrome P450]]

	==Reference==		==Reference==

OCA at 18:29, 2 May 2012

2012-05-02T18:29:28Z

← Older revision		Revision as of 18:29, 2 May 2012
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	[[Image:3tk3.~~jpg~~\|left\|200px]]		[[Image:3tk3.png\|left\|200px]]

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OCA at 12:19, 16 November 2011

2011-11-16T12:19:58Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:3tk3.jpg|left|200px]]
-The entry 3tk3 is ON HOLD  until Paper Publication
+<!--
-Authors: Gay, S.C., Jang, H.H., Wilderman, P.R., Zhang, Q., Stout, C.D., Halpert, J.R.
+===Cytochrome P450 2B4 mutant L437A in complex with 4-(4-chlorophenyl)imidazole===
-Description: Cytochrome P450 2B4 mutant L437A in complex with 4-(4-chlorophenyl)imidazole