3swz - Revision history

OCA at 13:10, 14 March 2024

OCA — Thu, 14 Mar 2024 13:10:28 GMT

←Older revision		Revision as of 13:10, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3swz' size='340' side='right'caption='[[3swz]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='3swz' size='340' side='right'caption='[[3swz]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3swz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SWZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SWZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3swz]] is a 4 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=3SWZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SWZ FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=TOK:(3ALPHA,8ALPHA)~~-~~17-(1H-BENZIMIDAZOL-1-YL)ANDROSTA-5~~,~~16-DIEN-3-OL'>TOK</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]] 2.4Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>~~[[~~Related_structure~~\|~~Related:~~]]~~</b></td><td class="sblockDat"><div style='overflow: auto~~; ~~max-height: 3em;'>[[3ruk\|3ruk]]</div>~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=TOK:(3ALPHA,8ALPHA)-17-(1H-BENZIMIDAZOL-1-YL)ANDROSTA-5,16-DIEN-3-OL'>TOK</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>CYP17, CYP17A1, S17AH ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9606 HUMAN])</td~~><~~/tr>~~	+
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[https~~:~~//en.wikipedia.org/wiki/Steroid_17-alpha~~-~~monooxygenase Steroid~~ 17-~~alpha~~-~~monooxygenase]~~, ~~with EC number [https://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=1.14.99.9 1.14.99.9]~~ </~~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=3swz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3swz OCA], [https://pdbe.org/3swz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3swz RCSB], [https://www.ebi.ac.uk/pdbsum/3swz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3swz 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=3swz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3swz OCA], [https://pdbe.org/3swz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3swz RCSB], [https://www.ebi.ac.uk/pdbsum/3swz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3swz ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/CP17A_HUMAN CP17A_HUMAN]] Congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency;46,XY disorder of sex development due to isolated 17, 20 lyase deficiency. The disease is caused by mutations affecting the gene represented in this entry.	+	[https://www.uniprot.org/uniprot/CP17A_HUMAN CP17A_HUMAN] Congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency;46,XY disorder of sex development due to isolated 17, 20 lyase deficiency. The disease is caused by mutations affecting the gene represented in this entry.
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/CP17A_HUMAN CP17A_HUMAN]] Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Involved in sexual development during fetal life and at puberty.<ref>PMID:22266943</ref>	+	[https://www.uniprot.org/uniprot/CP17A_HUMAN CP17A_HUMAN] Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Involved in sexual development during fetal life and at puberty.<ref>PMID:22266943</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Cytochrome P450 17A1 (also known as CYP17A1 and cytochrome P450c17) catalyses the biosynthesis of androgens in humans. As prostate cancer cells proliferate in response to androgen steroids, CYP17A1 inhibition is a new strategy to prevent androgen synthesis and treat lethal metastatic castration-resistant prostate cancer, but drug development has been hampered by lack of information regarding the structure of CYP17A1. Here we report X-ray crystal structures of CYP17A1, which were obtained in the presence of either abiraterone, a first-in-class steroidal inhibitor recently approved by the US Food and Drug Administration for late-stage prostate cancer, or TOK-001, an inhibitor that is currently undergoing clinical trials. Both of these inhibitors bind the haem iron, forming a 60 degrees angle above the haem plane and packing against the central I helix with the 3beta-OH interacting with aspargine 202 in the F helix. Notably, this binding mode differs substantially from those that are predicted by homology models and from steroids in other cytochrome P450 enzymes with known structures, and some features of this binding mode are more similar to steroid receptors. Whereas the overall structure of CYP17A1 provides a rationale for understanding many mutations that are found in patients with steroidogenic diseases, the active site reveals multiple steric and hydrogen bonding features that will facilitate a better understanding of the enzyme's dual hydroxylase and lyase catalytic capabilities and assist in rational drug design. Specifically, structure-based design is expected to aid development of inhibitors that bind only CYP17A1 and solely inhibit its androgen-generating lyase activity to improve treatment of prostate and other hormone-responsive cancers.	+
-		+
-	~~Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001.,Devore NM, Scott EE Nature. 2012 Jan 22. doi: 10.1038/nature10743. PMID:22266943<ref>PMID:22266943</ref>~~	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3swz" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 30:		Line 19:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Steroid 17-alpha-monooxygenase]]~~	+	[[Category: DeVore NM]]
-	[[Category: DeVore~~, N M~~]]	+	[[Category: Scott EE]]
-	[[Category: Scott~~, E E]]~~	+
-	~~[[Category: 17a-hydroxylase]]~~	+
-	~~[[Category: 20-lyase]]~~	+
-	~~[[Category: Cyp17a1]]~~	+
-	~~[[Category: Cytochrome p450]]~~	+
-	~~[[Category: Cytochrome p450 oxidoreductase]]~~	+
-	~~[[Category: Endoplasmic reticulum]]~~	+
-	~~[[Category: Galeterone]]~~	+
-	~~[[Category: Heme protein]]~~	+
-	~~[[Category: Membrane]]~~	+
-	~~[[Category: Microsome]]~~	+
-	~~[[Category: Monooxygenase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]~~	+
-	~~[[Category: P450]]~~	+
-	~~[[Category: P450 17a1]]~~	+
-	~~[[Category: P450c17]]~~	+
-	~~[[Category: Tok-001]]~~	+
-	~~[[Category: Vn/124-1~~]]	+

OCA at 08:14, 29 June 2022

OCA — Wed, 29 Jun 2022 08:14:05 GMT

←Older revision		Revision as of 08:14, 29 June 2022
Line 1:		Line 1:

	==Human Cytochrome P450 17A1 in complex with TOK-001==		==Human Cytochrome P450 17A1 in complex with TOK-001==
-	<StructureSection load='3swz' size='340' side='right' caption='[[3swz]], [[Resolution\|resolution]] 2.40Å' scene=''>	+	<StructureSection load='3swz' size='340' side='right'caption='[[3swz]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3swz]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SWZ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3SWZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3swz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SWZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SWZ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=TOK:(3ALPHA,8ALPHA)-17-(1H-BENZIMIDAZOL-1-YL)ANDROSTA-5,16-DIEN-3-OL'>TOK</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=TOK:(3ALPHA,8ALPHA)-17-(1H-BENZIMIDAZOL-1-YL)ANDROSTA-5,16-DIEN-3-OL'>TOK</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ruk\|3ruk]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ruk\|3ruk]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP17, CYP17A1, S17AH ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP17, CYP17A1, S17AH ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Steroid_17-alpha-monooxygenase Steroid 17-alpha-monooxygenase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.9 1.14.99.9] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Steroid_17-alpha-monooxygenase Steroid 17-alpha-monooxygenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.9 1.14.99.9] </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=3swz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3swz OCA], [~~http~~://pdbe.org/3swz PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3swz RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3swz PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3swz 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=3swz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3swz OCA], [https://pdbe.org/3swz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3swz RCSB], [https://www.ebi.ac.uk/pdbsum/3swz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3swz ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/CP17A_HUMAN CP17A_HUMAN]] Congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency;46,XY disorder of sex development due to isolated 17, 20 lyase deficiency. The disease is caused by mutations affecting the gene represented in this entry.	+	[[https://www.uniprot.org/uniprot/CP17A_HUMAN CP17A_HUMAN]] Congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency;46,XY disorder of sex development due to isolated 17, 20 lyase deficiency. The disease is caused by mutations affecting the gene represented in this entry.
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/CP17A_HUMAN CP17A_HUMAN]] Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Involved in sexual development during fetal life and at puberty.<ref>PMID:22266943</ref>	+	[[https://www.uniprot.org/uniprot/CP17A_HUMAN CP17A_HUMAN]] Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Involved in sexual development during fetal life and at puberty.<ref>PMID:22266943</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 23:
	</div>		</div>
	<div class="pdbe-citations 3swz" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3swz" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Cytochrome P450 3D structures\|Cytochrome P450 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 28:		Line 31:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Steroid 17-alpha-monooxygenase]]		[[Category: Steroid 17-alpha-monooxygenase]]
	[[Category: DeVore, N M]]		[[Category: DeVore, N M]]

OCA at 21:20, 4 August 2016

OCA — Thu, 04 Aug 2016 21:20:12 GMT

←Older revision		Revision as of 21:20, 4 August 2016
Line 1:		Line 1:
		+
	==Human Cytochrome P450 17A1 in complex with TOK-001==		==Human Cytochrome P450 17A1 in complex with TOK-001==
	<StructureSection load='3swz' size='340' side='right' caption='[[3swz]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='3swz' size='340' side='right' caption='[[3swz]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3swz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SWZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SWZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3swz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SWZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SWZ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=TOK:(3ALPHA,8ALPHA)-17-(1H-BENZIMIDAZOL-1-YL)ANDROSTA-5,16-DIEN-3-OL'>TOK</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=TOK:(3ALPHA,8ALPHA)-17-(1H-BENZIMIDAZOL-1-YL)ANDROSTA-5,16-DIEN-3-OL'>TOK</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ruk\|3ruk]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ruk\|3ruk]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP17, CYP17A1, S17AH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP17, CYP17A1, S17AH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Steroid_17-alpha-monooxygenase Steroid 17-alpha-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.9 1.14.99.9] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Steroid_17-alpha-monooxygenase Steroid 17-alpha-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.9 1.14.99.9] </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=3swz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3swz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3swz RCSB], [http://www.ebi.ac.uk/pdbsum/3swz 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=3swz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3swz OCA], [http://pdbe.org/3swz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3swz RCSB], [http://www.ebi.ac.uk/pdbsum/3swz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3swz ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	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 3swz" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Steroid 17-alpha-monooxygenase]]		[[Category: Steroid 17-alpha-monooxygenase]]
	[[Category: DeVore, N M]]		[[Category: DeVore, N M]]

OCA at 19:45, 24 December 2014

OCA — Wed, 24 Dec 2014 19:45:25 GMT

←Older revision		Revision as of 19:45, 24 December 2014
Line 1:		Line 1:
-	[[~~Image:~~3swz.~~png~~\|~~left~~\|~~200px~~]]	+	==Human Cytochrome P450 17A1 in complex with TOK-001==
		+	<StructureSection load='3swz' size='340' side='right' caption='[[3swz]], [[Resolution\|resolution]] 2.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3swz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SWZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SWZ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=TOK:(3ALPHA,8ALPHA)-17-(1H-BENZIMIDAZOL-1-YL)ANDROSTA-5,16-DIEN-3-OL'>TOK</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ruk\|3ruk]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CYP17, CYP17A1, S17AH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Steroid_17-alpha-monooxygenase Steroid 17-alpha-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.9 1.14.99.9] </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=3swz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3swz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3swz RCSB], [http://www.ebi.ac.uk/pdbsum/3swz PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/CP17A_HUMAN CP17A_HUMAN]] Congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency;46,XY disorder of sex development due to isolated 17, 20 lyase deficiency. The disease is caused by mutations affecting the gene represented in this entry.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CP17A_HUMAN CP17A_HUMAN]] Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Involved in sexual development during fetal life and at puberty.<ref>PMID:22266943</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Cytochrome P450 17A1 (also known as CYP17A1 and cytochrome P450c17) catalyses the biosynthesis of androgens in humans. As prostate cancer cells proliferate in response to androgen steroids, CYP17A1 inhibition is a new strategy to prevent androgen synthesis and treat lethal metastatic castration-resistant prostate cancer, but drug development has been hampered by lack of information regarding the structure of CYP17A1. Here we report X-ray crystal structures of CYP17A1, which were obtained in the presence of either abiraterone, a first-in-class steroidal inhibitor recently approved by the US Food and Drug Administration for late-stage prostate cancer, or TOK-001, an inhibitor that is currently undergoing clinical trials. Both of these inhibitors bind the haem iron, forming a 60 degrees angle above the haem plane and packing against the central I helix with the 3beta-OH interacting with aspargine 202 in the F helix. Notably, this binding mode differs substantially from those that are predicted by homology models and from steroids in other cytochrome P450 enzymes with known structures, and some features of this binding mode are more similar to steroid receptors. Whereas the overall structure of CYP17A1 provides a rationale for understanding many mutations that are found in patients with steroidogenic diseases, the active site reveals multiple steric and hydrogen bonding features that will facilitate a better understanding of the enzyme's dual hydroxylase and lyase catalytic capabilities and assist in rational drug design. Specifically, structure-based design is expected to aid development of inhibitors that bind only CYP17A1 and solely inhibit its androgen-generating lyase activity to improve treatment of prostate and other hormone-responsive cancers.

-	<!--	+	Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001.,Devore NM, Scott EE Nature. 2012 Jan 22. doi: 10.1038/nature10743. PMID:22266943<ref>PMID:22266943</ref>
-	~~The line below this paragraph~~, ~~containing "STRUCTURE_3swz"~~, ~~creates the "Structure Box" on the page~~.	+
-	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~	+
-	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~	+
-	~~or leave the SCENE parameter empty for the default display~~.	+
-	-->	+
-	~~{{STRUCTURE_3swz\| PDB=3swz \| SCENE= }}~~	+

-	~~===Human Cytochrome P450 17A1 in complex with TOK-001===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-		+	== References ==
-	~~<!--~~	+	<references/>
-	~~The line below this paragraph~~, ~~{{ABSTRACT_PUBMED_22266943}}, adds~~ the ~~Publication Abstract to the page~~	+	__TOC__
-	~~(as it appears on PubMed at http://www~~.~~pubmed~~.~~gov), where 22266943 is the PubMed ID number~~.	+	</StructureSection>
-	-->	+
-	~~{{ABSTRACT_PUBMED_22266943}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3swz]] is a 4 chain structure with sequence from [http:~~/~~/en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SWZ OCA].~~	+
-		+
-	==~~Reference~~==	+
-	<~~ref group="xtra">PMID:022266943<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Steroid 17-alpha-monooxygenase]]		[[Category: Steroid 17-alpha-monooxygenase]]
-	[[Category: DeVore, N M.]]	+	[[Category: DeVore, N M]]
-	[[Category: Scott, E E~~.]]~~	+	[[Category: Scott, E E]]
-	~~[[Category: 17~~]]	+
	[[Category: 17a-hydroxylase]]		[[Category: 17a-hydroxylase]]
	[[Category: 20-lyase]]		[[Category: 20-lyase]]

OCA at 06:19, 1 February 2012

OCA — Wed, 01 Feb 2012 06:19:00 GMT

←Older revision		Revision as of 06:19, 1 February 2012
Line 1:		Line 1:
-	[[Image:3swz.~~jpg~~\|left\|200px]]	+	[[Image:3swz.png\|left\|200px]]

	<!--		<!--
Line 11:		Line 11:
	===Human Cytochrome P450 17A1 in complex with TOK-001===		===Human Cytochrome P450 17A1 in complex with TOK-001===

		+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22266943}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22266943 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22266943}}

	==About this Structure==		==About this Structure==
	[[3swz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SWZ OCA].		[[3swz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SWZ OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022266943</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Steroid 17-alpha-monooxygenase]]		[[Category: Steroid 17-alpha-monooxygenase]]

OCA at 06:43, 25 January 2012

OCA — Wed, 25 Jan 2012 06:43:51 GMT

←Older revision		Revision as of 06:43, 25 January 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3swz.jpg\|left\|200px]]

-	The ~~entry 3swz~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3swz", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3swz\| PDB=3swz \| SCENE= }}

-	~~Authors: DeVore, N.M., Scott, E.E.~~	+	===Human Cytochrome P450 17A1 in complex with TOK-001===

-	~~Description~~: ~~Human~~ Cytochrome ~~P450 17A1 in~~ complex ~~with TOK~~-001	+
		+	==About this Structure==
		+	[[3swz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SWZ OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Steroid 17-alpha-monooxygenase]]
		+	[[Category: DeVore, N M.]]
		+	[[Category: Scott, E E.]]
		+	[[Category: 17]]
		+	[[Category: 17a-hydroxylase]]
		+	[[Category: 20-lyase]]
		+	[[Category: Cyp17a1]]
		+	[[Category: Cytochrome p450]]
		+	[[Category: Cytochrome p450 oxidoreductase]]
		+	[[Category: Endoplasmic reticulum]]
		+	[[Category: Galeterone]]
		+	[[Category: Heme protein]]
		+	[[Category: Membrane]]
		+	[[Category: Microsome]]
		+	[[Category: Monooxygenase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
		+	[[Category: P450]]
		+	[[Category: P450 17a1]]
		+	[[Category: P450c17]]
		+	[[Category: Tok-001]]
		+	[[Category: Vn/124-1]]

OCA at 05:43, 7 September 2011

OCA — Wed, 07 Sep 2011 05:43:35 GMT

←Older revision		Revision as of 05:43, 7 September 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3swz is ON HOLD	+	The entry 3swz is ON HOLD until Paper Publication

	Authors: DeVore, N.M., Scott, E.E.		Authors: DeVore, N.M., Scott, E.E.

	Description: Human Cytochrome P450 17A1 in complex with TOK-001		Description: Human Cytochrome P450 17A1 in complex with TOK-001

OCA: Protected "3swz" [edit=sysop:move=sysop]

OCA — Wed, 20 Jul 2011 06:19:51 GMT

Protected "3swz" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:19, 20 July 2011

OCA: New page: '''Unreleased structure''' The entry 3swz is ON HOLD Authors: DeVore, N.M., Scott, E.E. Description: Human Cytochrome P450 17A1 in complex with TOK-001

OCA — Wed, 20 Jul 2011 06:19:50 GMT

New page: '''Unreleased structure''' The entry 3swz is ON HOLD Authors: DeVore, N.M., Scott, E.E. Description: Human Cytochrome P450 17A1 in complex with TOK-001

New page

'''Unreleased structure'''

The entry 3swz is ON HOLD

Authors: DeVore, N.M., Scott, E.E.

Description: Human Cytochrome P450 17A1 in complex with TOK-001