4rfr - Revision history

OCA at 12:52, 1 March 2024

2024-03-01T12:52:06Z

←Older revision		Revision as of 12:52, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4rfr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RFR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RFR FirstGlance]. <br>		<table><tr><td colspan='2'>[[4rfr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RFR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RFR FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=RHN:4,5-DIHYDROXY-9,10-DIOXO-9,10-DIHYDROANTHRACENE-2-CARBOXYLIC+ACID'>RHN</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]] 1.5Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=RHN:4,5-DIHYDROXY-9,10-DIOXO-9,10-DIHYDROANTHRACENE-2-CARBOXYLIC+ACID'>RHN</scene></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=4rfr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rfr OCA], [https://pdbe.org/4rfr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rfr RCSB], [https://www.ebi.ac.uk/pdbsum/4rfr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rfr 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=4rfr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rfr OCA], [https://pdbe.org/4rfr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rfr RCSB], [https://www.ebi.ac.uk/pdbsum/4rfr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rfr ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/ALKB_ECOLI ALKB_ECOLI] Dioxygenase that repairs alkylated DNA and RNA containing 3-methylcytosine or 1-methyladenine by oxidative demethylation. Has highest activity towards 3-methylcytosine. Has lower activity towards alkylated DNA containing ethenoadenine, and no detectable activity towards 1-methylguanine or 3-methylthymine. Accepts double-stranded and single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron. Provides extensive resistance to alkylating agents such as MMS and DMS (SN2 agents), but not to MMNG and MNU (SN1 agents).<ref>PMID:12226668</ref> <ref>PMID:12594517</ref> <ref>PMID:16482161</ref> <ref>PMID:19706517</ref> <ref>PMID:21068844</ref> <ref>PMID:20084272</ref>		[https://www.uniprot.org/uniprot/ALKB_ECOLI ALKB_ECOLI] Dioxygenase that repairs alkylated DNA and RNA containing 3-methylcytosine or 1-methyladenine by oxidative demethylation. Has highest activity towards 3-methylcytosine. Has lower activity towards alkylated DNA containing ethenoadenine, and no detectable activity towards 1-methylguanine or 3-methylthymine. Accepts double-stranded and single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron. Provides extensive resistance to alkylating agents such as MMS and DMS (SN2 agents), but not to MMNG and MNU (SN1 agents).<ref>PMID:12226668</ref> <ref>PMID:12594517</ref> <ref>PMID:16482161</ref> <ref>PMID:19706517</ref> <ref>PMID:21068844</ref> <ref>PMID:20084272</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The AlkB repair enzymes, including Escherichia coli AlkB and two human homologues, ALKBH2 and ALKBH3, are iron(II)- and 2-oxoglutarate-dependent dioxygenases that efficiently repair N(1)-methyladenine and N(3)-methylcytosine methylated DNA damages. The development of small molecule inhibitors of these enzymes has seen less success. Here we have characterized a previously discovered natural product rhein and tested its ability to inhibit AlkB repair enzymes in vitro and to sensitize cells to methyl methane sulfonate that mainly produces N(1)-methyladenine and N(3)-methylcytosine lesions. Our investigation of the mechanism of rhein inhibition reveals that rhein binds to AlkB repair enzymes in vitro and promotes thermal stability in vivo In addition, we have determined a new structural complex of rhein bound to AlkB, which shows that rhein binds to a different part of the active site in AlkB than it binds to in fat mass and obesity-associated protein (FTO). With the support of these observations, we put forth the hypothesis that AlkB repair enzymes would be effective pharmacological targets for cancer treatment.
-
-	Rhein Inhibits AlkB Repair Enzymes and Sensitizes Cells to Methylated DNA Damage.,Li Q, Huang Y, Liu X, Gan J, Chen H, Yang CG J Biol Chem. 2016 May 20;291(21):11083-93. doi: 10.1074/jbc.M115.711895. Epub, 2016 Mar 25. PMID:27015802<ref>PMID:27015802</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4rfr" style="background-color:#fffaf0;"></div>

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

OCA at 06:53, 2 March 2023

2023-03-02T06:53:53Z

←Older revision		Revision as of 06:53, 2 March 2023
Line 3:		Line 3:
	<StructureSection load='4rfr' size='340' side='right'caption='[[4rfr]], [[Resolution\|resolution]] 1.50Å' scene=''>		<StructureSection load='4rfr' size='340' side='right'caption='[[4rfr]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4rfr]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"bacillus_coli"_migula_1895 "bacillus~~ coli~~" migula 1895~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RFR OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4RFR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4rfr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RFR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RFR FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=RHN:4,5-DIHYDROXY-9,10-DIOXO-9,10-DIHYDROANTHRACENE-2-CARBOXYLIC+ACID'>RHN</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=RHN:4,5-DIHYDROXY-9,10-DIOXO-9,10-DIHYDROANTHRACENE-2-CARBOXYLIC+ACID'>RHN</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3t4h\|3t4h]]</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=4rfr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rfr OCA], [https://pdbe.org/4rfr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rfr RCSB], [https://www.ebi.ac.uk/pdbsum/4rfr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rfr ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">alkB, aidD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_oxidative_demethylase DNA oxidative demethylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.33 1.14.11.33] </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=4rfr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rfr OCA], [~~http~~://pdbe.org/4rfr PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4rfr RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4rfr PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4rfr ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ALKB_ECOLI ALKB_ECOLI]] Dioxygenase that repairs alkylated DNA and RNA containing 3-methylcytosine or 1-methyladenine by oxidative demethylation. Has highest activity towards 3-methylcytosine. Has lower activity towards alkylated DNA containing ethenoadenine, and no detectable activity towards 1-methylguanine or 3-methylthymine. Accepts double-stranded and single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron. Provides extensive resistance to alkylating agents such as MMS and DMS (SN2 agents), but not to MMNG and MNU (SN1 agents).<ref>PMID:12226668</ref> <ref>PMID:12594517</ref> <ref>PMID:16482161</ref> <ref>PMID:19706517</ref> <ref>PMID:21068844</ref> <ref>PMID:20084272</ref>	+	[https://www.uniprot.org/uniprot/ALKB_ECOLI ALKB_ECOLI] Dioxygenase that repairs alkylated DNA and RNA containing 3-methylcytosine or 1-methyladenine by oxidative demethylation. Has highest activity towards 3-methylcytosine. Has lower activity towards alkylated DNA containing ethenoadenine, and no detectable activity towards 1-methylguanine or 3-methylthymine. Accepts double-stranded and single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron. Provides extensive resistance to alkylating agents such as MMS and DMS (SN2 agents), but not to MMNG and MNU (SN1 agents).<ref>PMID:12226668</ref> <ref>PMID:12594517</ref> <ref>PMID:16482161</ref> <ref>PMID:19706517</ref> <ref>PMID:21068844</ref> <ref>PMID:20084272</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 20:

	==See Also==		==See Also==
-	*[[Dioxygenase\|Dioxygenase]]	+	*[[Dioxygenase 3D structures\|Dioxygenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bacillus~~ coli ~~migula 1895]]~~	+	[[Category: Escherichia coli]]
-	~~[[Category: DNA oxidative demethylase~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Huang, Y]]	+	[[Category: Huang Y]]
-	[[Category: Li~~, J F~~]]	+	[[Category: Li JF]]
-	[[Category: Li, Q]]	+	[[Category: Li Q]]
-	[[Category: Yang, C G]]	+	[[Category: Yang C-G]]
-	~~[[Category: Alkb family]]~~	+
-	~~[[Category: Demethylase]]~~	+
-	~~[[Category: Demethylation]]~~	+
-	~~[[Category: Jellyroll fold]]~~	+
-	~~[[Category: Nucleic acid binding]]~~	+
-	~~[[Category: Nucleus]]~~	+
-	~~[[Category: Oxidoreductase-inhibitor complex]]~~	+
-	~~[[Category: Protein-inhibitor complex~~]]	+

OCA at 10:02, 1 May 2019

2019-05-01T10:02:23Z

←Older revision		Revision as of 10:02, 1 May 2019
Line 1:		Line 1:

	==Complex structure of AlkB/rhein==		==Complex structure of AlkB/rhein==
-	<StructureSection load='4rfr' size='340' side='right' caption='[[4rfr]], [[Resolution\|resolution]] 1.50Å' scene=''>	+	<StructureSection load='4rfr' size='340' side='right'caption='[[4rfr]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4rfr]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RFR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RFR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4rfr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RFR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RFR FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=RHN:4,5-DIHYDROXY-9,10-DIOXO-9,10-DIHYDROANTHRACENE-2-CARBOXYLIC+ACID'>RHN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=RHN:4,5-DIHYDROXY-9,10-DIOXO-9,10-DIHYDROANTHRACENE-2-CARBOXYLIC+ACID'>RHN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3t4h\|3t4h]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3t4h\|3t4h]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">alkB, aidD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_oxidative_demethylase DNA oxidative demethylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.33 1.14.11.33] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_oxidative_demethylase DNA oxidative demethylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.33 1.14.11.33] </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=4rfr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rfr OCA], [http://pdbe.org/4rfr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rfr RCSB], [http://www.ebi.ac.uk/pdbsum/4rfr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rfr ProSAT]</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=4rfr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rfr OCA], [http://pdbe.org/4rfr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rfr RCSB], [http://www.ebi.ac.uk/pdbsum/4rfr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rfr ProSAT]</span></td></tr>
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 4rfr" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4rfr" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dioxygenase\|Dioxygenase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Bacillus coli migula 1895]]
	[[Category: DNA oxidative demethylase]]		[[Category: DNA oxidative demethylase]]
		+	[[Category: Large Structures]]
	[[Category: Huang, Y]]		[[Category: Huang, Y]]
	[[Category: Li, J F]]		[[Category: Li, J F]]

OCA at 09:28, 3 October 2016

2016-10-03T09:28:04Z

←Older revision		Revision as of 09:28, 3 October 2016
Line 7:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3t4h\|3t4h]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3t4h\|3t4h]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_oxidative_demethylase DNA oxidative demethylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.33 1.14.11.33] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_oxidative_demethylase DNA oxidative demethylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.33 1.14.11.33] </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=4rfr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rfr OCA], [http://pdbe.org/4rfr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rfr RCSB], [http://www.ebi.ac.uk/pdbsum/4rfr 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=4rfr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rfr OCA], [http://pdbe.org/4rfr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rfr RCSB], [http://www.ebi.ac.uk/pdbsum/4rfr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rfr ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/ALKB_ECOLI ALKB_ECOLI]] Dioxygenase that repairs alkylated DNA and RNA containing 3-methylcytosine or 1-methyladenine by oxidative demethylation. Has highest activity towards 3-methylcytosine. Has lower activity towards alkylated DNA containing ethenoadenine, and no detectable activity towards 1-methylguanine or 3-methylthymine. Accepts double-stranded and single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron. Provides extensive resistance to alkylating agents such as MMS and DMS (SN2 agents), but not to MMNG and MNU (SN1 agents).<ref>PMID:12226668</ref> <ref>PMID:12594517</ref> <ref>PMID:16482161</ref> <ref>PMID:19706517</ref> <ref>PMID:21068844</ref> <ref>PMID:20084272</ref>		[[http://www.uniprot.org/uniprot/ALKB_ECOLI ALKB_ECOLI]] Dioxygenase that repairs alkylated DNA and RNA containing 3-methylcytosine or 1-methyladenine by oxidative demethylation. Has highest activity towards 3-methylcytosine. Has lower activity towards alkylated DNA containing ethenoadenine, and no detectable activity towards 1-methylguanine or 3-methylthymine. Accepts double-stranded and single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron. Provides extensive resistance to alkylating agents such as MMS and DMS (SN2 agents), but not to MMNG and MNU (SN1 agents).<ref>PMID:12226668</ref> <ref>PMID:12594517</ref> <ref>PMID:16482161</ref> <ref>PMID:19706517</ref> <ref>PMID:21068844</ref> <ref>PMID:20084272</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The AlkB repair enzymes, including Escherichia coli AlkB and two human homologues, ALKBH2 and ALKBH3, are iron(II)- and 2-oxoglutarate-dependent dioxygenases that efficiently repair N(1)-methyladenine and N(3)-methylcytosine methylated DNA damages. The development of small molecule inhibitors of these enzymes has seen less success. Here we have characterized a previously discovered natural product rhein and tested its ability to inhibit AlkB repair enzymes in vitro and to sensitize cells to methyl methane sulfonate that mainly produces N(1)-methyladenine and N(3)-methylcytosine lesions. Our investigation of the mechanism of rhein inhibition reveals that rhein binds to AlkB repair enzymes in vitro and promotes thermal stability in vivo In addition, we have determined a new structural complex of rhein bound to AlkB, which shows that rhein binds to a different part of the active site in AlkB than it binds to in fat mass and obesity-associated protein (FTO). With the support of these observations, we put forth the hypothesis that AlkB repair enzymes would be effective pharmacological targets for cancer treatment.
		+
		+	Rhein Inhibits AlkB Repair Enzymes and Sensitizes Cells to Methylated DNA Damage.,Li Q, Huang Y, Liu X, Gan J, Chen H, Yang CG J Biol Chem. 2016 May 20;291(21):11083-93. doi: 10.1074/jbc.M115.711895. Epub, 2016 Mar 25. PMID:27015802<ref>PMID:27015802</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 4rfr" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 04:01, 12 May 2016

2016-05-12T04:01:06Z

←Older revision		Revision as of 04:01, 12 May 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 4rfr ~~is ON HOLD until Paper Publication~~	+	==Complex structure of AlkB/rhein==
-		+	<StructureSection load='4rfr' size='340' side='right' caption='[[4rfr]], [[Resolution\|resolution]] 1.50Å' scene=''>
-	~~Authors~~: ~~Li, Q~~.~~, Huang, Y~~.~~, Li, J~~.F.~~, Yang, C~~.-G.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4rfr]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RFR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RFR FirstGlance]. <br>
-	~~Description~~: ~~Complex structure of AlkB~~/~~rhein~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=RHN:4,5-DIHYDROXY-9,10-DIOXO-9,10-DIHYDROANTHRACENE-2-CARBOXYLIC+ACID'>RHN</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3t4h\|3t4h]]</td></tr>
-	[[~~Category~~: Li, J.F]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_oxidative_demethylase DNA oxidative demethylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.33 1.14.11.33] </span></td></tr>
-	[[~~Category~~: ~~Yang~~, C.-G]]	+	<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=4rfr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rfr OCA], [http://pdbe.org/4rfr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rfr RCSB], [http://www.ebi.ac.uk/pdbsum/4rfr PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ALKB_ECOLI ALKB_ECOLI]] Dioxygenase that repairs alkylated DNA and RNA containing 3-methylcytosine or 1-methyladenine by oxidative demethylation. Has highest activity towards 3-methylcytosine. Has lower activity towards alkylated DNA containing ethenoadenine, and no detectable activity towards 1-methylguanine or 3-methylthymine. Accepts double-stranded and single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron. Provides extensive resistance to alkylating agents such as MMS and DMS (SN2 agents), but not to MMNG and MNU (SN1 agents).<ref>PMID:12226668</ref> <ref>PMID:12594517</ref> <ref>PMID:16482161</ref> <ref>PMID:19706517</ref> <ref>PMID:21068844</ref> <ref>PMID:20084272</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: DNA oxidative demethylase]]
	[[Category: Huang, Y]]		[[Category: Huang, Y]]
		+	[[Category: Li, J F]]
	[[Category: Li, Q]]		[[Category: Li, Q]]
		+	[[Category: Yang, C G]]
		+	[[Category: Alkb family]]
		+	[[Category: Demethylase]]
		+	[[Category: Demethylation]]
		+	[[Category: Jellyroll fold]]
		+	[[Category: Nucleic acid binding]]
		+	[[Category: Nucleus]]
		+	[[Category: Oxidoreductase-inhibitor complex]]
		+	[[Category: Protein-inhibitor complex]]

OCA at 16:49, 24 December 2014

2014-12-24T16:49:39Z

←Older revision		Revision as of 16:49, 24 December 2014
Line 6:		Line 6:

	Description: Complex structure of AlkB/rhein		Description: Complex structure of AlkB/rhein
		+	[[Category: Unreleased Structures]]
		+	[[Category: Li, J.F]]
		+	[[Category: Yang, C.-G]]
		+	[[Category: Huang, Y]]
		+	[[Category: Li, Q]]

OCA at 09:27, 20 October 2014

2014-10-20T09:27:38Z

←Older revision		Revision as of 09:27, 20 October 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4rfr is ON HOLD	+	The entry 4rfr is ON HOLD until Paper Publication

	Authors: Li, Q., Huang, Y., Li, J.F., Yang, C.-G.		Authors: Li, Q., Huang, Y., Li, J.F., Yang, C.-G.

	Description: Complex structure of AlkB/rhein		Description: Complex structure of AlkB/rhein

OCA: Protected "4rfr" [edit=sysop:move=sysop]

2014-10-08T06:33:05Z

Protected "4rfr" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:33, 8 October 2014

OCA: New page: '''Unreleased structure''' The entry 4rfr is ON HOLD Authors: Li, Q., Huang, Y., Li, J.F., Yang, C.-G. Description: Complex structure of AlkB/rhein

2014-10-08T06:33:04Z

New page: '''Unreleased structure''' The entry 4rfr is ON HOLD Authors: Li, Q., Huang, Y., Li, J.F., Yang, C.-G. Description: Complex structure of AlkB/rhein

New page

'''Unreleased structure'''

The entry 4rfr is ON HOLD

Authors: Li, Q., Huang, Y., Li, J.F., Yang, C.-G.

Description: Complex structure of AlkB/rhein