4qkn - Revision history

OCA at 19:24, 29 May 2024

OCA — Wed, 29 May 2024 19:24:40 GMT

←Older revision		Revision as of 19:24, 29 May 2024
Line 1:		Line 1:

	==Crystal structure of FTO bound to a selective inhibitor==		==Crystal structure of FTO bound to a selective inhibitor==
-	<StructureSection load='4qkn' size='340' side='right'caption='[[4qkn]]' scene=''>	+	<StructureSection load='4qkn' size='340' side='right'caption='[[4qkn]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QKN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qkn]] is a 1 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=4QKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QKN FirstGlance]. <br>
-	</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=4qkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qkn OCA], [https://pdbe.org/4qkn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qkn RCSB], [https://www.ebi.ac.uk/pdbsum/4qkn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qkn ProSAT]</span></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]] 2.2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JMS:2-[(2,6-DICHLORO-3-METHYL-PHENYL)AMINO]BENZOIC+ACID'>JMS</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</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=4qkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qkn OCA], [https://pdbe.org/4qkn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qkn RCSB], [https://www.ebi.ac.uk/pdbsum/4qkn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qkn ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/FTO_HUMAN FTO_HUMAN] Defects in FTO are the cause of growth retardation developmental delay coarse facies and early death (GDFD) [MIM:[https://omim.org/entry/612938 612938]. A severe polymalformation syndrome characterized by postnatal growth retardation, microcephaly, severe psychomotor delay, functional brain deficits and characteristic facial dysmorphism. In some patients, structural brain malformations, cardiac defects, genital anomalies, and cleft palate are observed. Early death occurs by the age of 3 years.<ref>PMID:19559399</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/FTO_HUMAN FTO_HUMAN] Dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation. Has highest activity towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine. Has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine. Has no activity towards 1-methylguanine. Has no detectable activity towards double-stranded DNA. Requires molecular oxygen, alpha-ketoglutarate and iron. Contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis. Contributes to the regulation of body size and body fat accumulation.<ref>PMID:18775698</ref> <ref>PMID:20376003</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Two human demethylases, the fat mass and obesity-associated (FTO) enzyme and ALKBH5, oxidatively demethylate abundant N6-methyladenosine (m6A) residues in mRNA. Achieving a method for selective inhibition of FTO over ALKBH5 remains a challenge, however. Here, we have identified meclofenamic acid (MA) as a highly selective inhibitor of FTO. MA is a non-steroidal, anti-inflammatory drug that mechanistic studies indicate competes with FTO binding for the m6A-containing nucleic acid. The structure of FTO/MA has revealed much about the inhibitory function of FTO. Our newfound understanding, revealed herein, of the part of the nucleotide recognition lid (NRL) in FTO, for example, has helped elucidate the principles behind the selectivity of FTO over ALKBH5. Treatment of HeLa cells with the ethyl ester form of MA (MA2) has led to elevated levels of m6A modification in mRNA. Our collective results highlight the development of functional probes of the FTO enzyme that will (i) enable future biological studies and (ii) pave the way for the rational design of potent and specific inhibitors of FTO for use in medicine.
		+
		+	Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5.,Huang Y, Yan J, Li Q, Li J, Gong S, Zhou H, Gan J, Jiang H, Jia GF, Luo C, Yang CG Nucleic Acids Res. 2014 Dec 1. pii: gku1276. PMID:25452335<ref>PMID:25452335</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 4qkn" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Dioxygenase 3D structures\|Dioxygenase 3D structures]]		*[[Dioxygenase 3D structures\|Dioxygenase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Gan J]]		[[Category: Gan J]]
	[[Category: Huang Y]]		[[Category: Huang Y]]
	[[Category: Yang C-G]]		[[Category: Yang C-G]]

OCA at 10:55, 31 August 2022

OCA — Wed, 31 Aug 2022 10:55:01 GMT

←Older revision		Revision as of 10:55, 31 August 2022
Line 1:		Line 1:

	==Crystal structure of FTO bound to a selective inhibitor==		==Crystal structure of FTO bound to a selective inhibitor==
-	<StructureSection load='4qkn' size='340' side='right'caption='[[4qkn]]~~, [[Resolution\|resolution]] 2.20Å~~' scene=''>	+	<StructureSection load='4qkn' size='340' side='right'caption='[[4qkn]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>~~[[4qkn]] is a 1 chain structure.~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QKN FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QKN FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JMS:2-[(2,6-DICHLORO-3-METHYL-PHENYL)AMINO]BENZOIC+ACID'>JMS</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene></td></tr>	+	</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=4qkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qkn OCA], [https://pdbe.org/4qkn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qkn RCSB], [https://www.ebi.ac.uk/pdbsum/4qkn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qkn 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=4qkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qkn OCA], [https://pdbe.org/4qkn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qkn RCSB], [https://www.ebi.ac.uk/pdbsum/4qkn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qkn ProSAT]</span></td></tr>	+
	</table>		</table>
-	== Disease ==
-	[[https://www.uniprot.org/uniprot/FTO_HUMAN FTO_HUMAN]] Defects in FTO are the cause of growth retardation developmental delay coarse facies and early death (GDFD) [MIM:[https://omim.org/entry/612938 612938]]. A severe polymalformation syndrome characterized by postnatal growth retardation, microcephaly, severe psychomotor delay, functional brain deficits and characteristic facial dysmorphism. In some patients, structural brain malformations, cardiac defects, genital anomalies, and cleft palate are observed. Early death occurs by the age of 3 years.<ref>PMID:19559399</ref>
-	== Function ==
-	[[https://www.uniprot.org/uniprot/FTO_HUMAN FTO_HUMAN]] Dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation. Has highest activity towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine. Has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine. Has no activity towards 1-methylguanine. Has no detectable activity towards double-stranded DNA. Requires molecular oxygen, alpha-ketoglutarate and iron. Contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis. Contributes to the regulation of body size and body fat accumulation.<ref>PMID:18775698</ref> <ref>PMID:20376003</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Two human demethylases, the fat mass and obesity-associated (FTO) enzyme and ALKBH5, oxidatively demethylate abundant N6-methyladenosine (m6A) residues in mRNA. Achieving a method for selective inhibition of FTO over ALKBH5 remains a challenge, however. Here, we have identified meclofenamic acid (MA) as a highly selective inhibitor of FTO. MA is a non-steroidal, anti-inflammatory drug that mechanistic studies indicate competes with FTO binding for the m6A-containing nucleic acid. The structure of FTO/MA has revealed much about the inhibitory function of FTO. Our newfound understanding, revealed herein, of the part of the nucleotide recognition lid (NRL) in FTO, for example, has helped elucidate the principles behind the selectivity of FTO over ALKBH5. Treatment of HeLa cells with the ethyl ester form of MA (MA2) has led to elevated levels of m6A modification in mRNA. Our collective results highlight the development of functional probes of the FTO enzyme that will (i) enable future biological studies and (ii) pave the way for the rational design of potent and specific inhibitors of FTO for use in medicine.
-
-	Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5.,Huang Y, Yan J, Li Q, Li J, Gong S, Zhou H, Gan J, Jiang H, Jia GF, Luo C, Yang CG Nucleic Acids Res. 2014 Dec 1. pii: gku1276. PMID:25452335<ref>PMID:25452335</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4qkn" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Dioxygenase 3D structures\|Dioxygenase 3D structures]]		*[[Dioxygenase 3D structures\|Dioxygenase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Gan, J]]	+	[[Category: Gan J]]
-	[[Category: Huang, Y]]	+	[[Category: Huang Y]]
-	[[Category: Yang, C G]]	+	[[Category: Yang C-G]]
-	~~[[Category: Jellyroll folding]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 05:07, 25 August 2022

OCA — Thu, 25 Aug 2022 05:07:01 GMT

←Older revision		Revision as of 05:07, 25 August 2022
Line 3:		Line 3:
	<StructureSection load='4qkn' size='340' side='right'caption='[[4qkn]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='4qkn' size='340' side='right'caption='[[4qkn]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4qkn]] is a 1 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=4QKN OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4QKN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qkn]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QKN FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JMS:2-[(2,6-DICHLORO-3-METHYL-PHENYL)AMINO]BENZOIC+ACID'>JMS</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JMS:2-[(2,6-DICHLORO-3-METHYL-PHENYL)AMINO]BENZOIC+ACID'>JMS</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FTO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</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=4qkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qkn OCA], [https://pdbe.org/4qkn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qkn RCSB], [https://www.ebi.ac.uk/pdbsum/4qkn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qkn 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=4qkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qkn OCA], [~~http~~://pdbe.org/4qkn PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4qkn RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4qkn PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4qkn ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/FTO_HUMAN FTO_HUMAN]] Defects in FTO are the cause of growth retardation developmental delay coarse facies and early death (GDFD) [MIM:[~~http~~://omim.org/entry/612938 612938]]. A severe polymalformation syndrome characterized by postnatal growth retardation, microcephaly, severe psychomotor delay, functional brain deficits and characteristic facial dysmorphism. In some patients, structural brain malformations, cardiac defects, genital anomalies, and cleft palate are observed. Early death occurs by the age of 3 years.<ref>PMID:19559399</ref>	+	[[https://www.uniprot.org/uniprot/FTO_HUMAN FTO_HUMAN]] Defects in FTO are the cause of growth retardation developmental delay coarse facies and early death (GDFD) [MIM:[https://omim.org/entry/612938 612938]]. A severe polymalformation syndrome characterized by postnatal growth retardation, microcephaly, severe psychomotor delay, functional brain deficits and characteristic facial dysmorphism. In some patients, structural brain malformations, cardiac defects, genital anomalies, and cleft palate are observed. Early death occurs by the age of 3 years.<ref>PMID:19559399</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/FTO_HUMAN FTO_HUMAN]] Dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation. Has highest activity towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine. Has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine. Has no activity towards 1-methylguanine. Has no detectable activity towards double-stranded DNA. Requires molecular oxygen, alpha-ketoglutarate and iron. Contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis. Contributes to the regulation of body size and body fat accumulation.<ref>PMID:18775698</ref> <ref>PMID:20376003</ref>	+	[[https://www.uniprot.org/uniprot/FTO_HUMAN FTO_HUMAN]] Dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation. Has highest activity towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine. Has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine. Has no activity towards 1-methylguanine. Has no detectable activity towards double-stranded DNA. Requires molecular oxygen, alpha-ketoglutarate and iron. Contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis. Contributes to the regulation of body size and body fat accumulation.<ref>PMID:18775698</ref> <ref>PMID:20376003</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 22:

	==See Also==		==See Also==
-	*[[Dioxygenase\|Dioxygenase]]	+	*[[Dioxygenase 3D structures\|Dioxygenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Gan, J]]		[[Category: Gan, J]]

OCA at 08:35, 24 April 2019

OCA — Wed, 24 Apr 2019 08:35:32 GMT

←Older revision		Revision as of 08:35, 24 April 2019
Line 1:		Line 1:

	==Crystal structure of FTO bound to a selective inhibitor==		==Crystal structure of FTO bound to a selective inhibitor==
-	<StructureSection load='4qkn' size='340' side='right' caption='[[4qkn]], [[Resolution\|resolution]] 2.20Å' scene=''>	+	<StructureSection load='4qkn' size='340' side='right'caption='[[4qkn]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4qkn]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QKN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QKN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qkn]] is a 1 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=4QKN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QKN FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JMS:2-[(2,6-DICHLORO-3-METHYL-PHENYL)AMINO]BENZOIC+ACID'>JMS</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JMS:2-[(2,6-DICHLORO-3-METHYL-PHENYL)AMINO]BENZOIC+ACID'>JMS</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FTO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4qkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qkn OCA], [http://pdbe.org/4qkn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qkn RCSB], [http://www.ebi.ac.uk/pdbsum/4qkn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qkn 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=4qkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qkn OCA], [http://pdbe.org/4qkn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qkn RCSB], [http://www.ebi.ac.uk/pdbsum/4qkn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qkn ProSAT]</span></td></tr>
	</table>		</table>
Line 27:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Gan, J]]		[[Category: Gan, J]]
	[[Category: Huang, Y]]		[[Category: Huang, Y]]

OCA at 14:31, 4 August 2016

OCA — Thu, 04 Aug 2016 14:31:40 GMT

←Older revision		Revision as of 14:31, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of FTO bound to a selective inhibitor==		==Crystal structure of FTO bound to a selective inhibitor==
	<StructureSection load='4qkn' size='340' side='right' caption='[[4qkn]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='4qkn' size='340' side='right' caption='[[4qkn]], [[Resolution\|resolution]] 2.20Å' scene=''>
Line 4:		Line 5:
	<table><tr><td colspan='2'>[[4qkn]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QKN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QKN FirstGlance]. <br>		<table><tr><td colspan='2'>[[4qkn]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QKN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QKN FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JMS:2-[(2,6-DICHLORO-3-METHYL-PHENYL)AMINO]BENZOIC+ACID'>JMS</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JMS:2-[(2,6-DICHLORO-3-METHYL-PHENYL)AMINO]BENZOIC+ACID'>JMS</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</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=4qkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qkn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qkn RCSB], [http://www.ebi.ac.uk/pdbsum/4qkn 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=4qkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qkn OCA], [http://pdbe.org/4qkn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qkn RCSB], [http://www.ebi.ac.uk/pdbsum/4qkn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qkn ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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 4qkn" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dioxygenase\|Dioxygenase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:48, 24 December 2014

OCA — Wed, 24 Dec 2014 10:48:04 GMT

←Older revision		Revision as of 10:48, 24 December 2014
Line 10:		Line 10:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/FTO_HUMAN FTO_HUMAN]] Dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation. Has highest activity towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine. Has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine. Has no activity towards 1-methylguanine. Has no detectable activity towards double-stranded DNA. Requires molecular oxygen, alpha-ketoglutarate and iron. Contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis. Contributes to the regulation of body size and body fat accumulation.<ref>PMID:18775698</ref> <ref>PMID:20376003</ref>		[[http://www.uniprot.org/uniprot/FTO_HUMAN FTO_HUMAN]] Dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation. Has highest activity towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine. Has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine. Has no activity towards 1-methylguanine. Has no detectable activity towards double-stranded DNA. Requires molecular oxygen, alpha-ketoglutarate and iron. Contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis. Contributes to the regulation of body size and body fat accumulation.<ref>PMID:18775698</ref> <ref>PMID:20376003</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Two human demethylases, the fat mass and obesity-associated (FTO) enzyme and ALKBH5, oxidatively demethylate abundant N6-methyladenosine (m6A) residues in mRNA. Achieving a method for selective inhibition of FTO over ALKBH5 remains a challenge, however. Here, we have identified meclofenamic acid (MA) as a highly selective inhibitor of FTO. MA is a non-steroidal, anti-inflammatory drug that mechanistic studies indicate competes with FTO binding for the m6A-containing nucleic acid. The structure of FTO/MA has revealed much about the inhibitory function of FTO. Our newfound understanding, revealed herein, of the part of the nucleotide recognition lid (NRL) in FTO, for example, has helped elucidate the principles behind the selectivity of FTO over ALKBH5. Treatment of HeLa cells with the ethyl ester form of MA (MA2) has led to elevated levels of m6A modification in mRNA. Our collective results highlight the development of functional probes of the FTO enzyme that will (i) enable future biological studies and (ii) pave the way for the rational design of potent and specific inhibitors of FTO for use in medicine.
		+
		+	Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5.,Huang Y, Yan J, Li Q, Li J, Gong S, Zhou H, Gan J, Jiang H, Jia GF, Luo C, Yang CG Nucleic Acids Res. 2014 Dec 1. pii: gku1276. PMID:25452335<ref>PMID:25452335</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 09:42, 3 December 2014

OCA — Wed, 03 Dec 2014 09:42:15 GMT

←Older revision		Revision as of 09:42, 3 December 2014
Line 1:		Line 1:
-	'''~~Unreleased structure~~'''	+	==Crystal structure of FTO bound to a selective inhibitor==
-		+	<StructureSection load='4qkn' size='340' side='right' caption='[[4qkn]], [[Resolution\|resolution]] 2.20Å' scene=''>
-	~~The entry~~ 4qkn is ~~ON HOLD until Paper Publication~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4qkn]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QKN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QKN FirstGlance]. <br>
-	~~Authors~~: ~~Yang~~, C.-G., ~~Huang~~, Y., ~~Gan~~, J.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JMS:2-[(2,6-DICHLORO-3-METHYL-PHENYL)AMINO]BENZOIC+ACID'>JMS</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</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=4qkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qkn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qkn RCSB], [http://www.ebi.ac.uk/pdbsum/4qkn PDBsum]</span></td></tr>
-	~~Description~~: ~~Crystal structure~~ of ~~FTO bound~~ to ~~a selective~~ inhibitor	+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/FTO_HUMAN FTO_HUMAN]] Defects in FTO are the cause of growth retardation developmental delay coarse facies and early death (GDFD) [MIM:[http://omim.org/entry/612938 612938]]. A severe polymalformation syndrome characterized by postnatal growth retardation, microcephaly, severe psychomotor delay, functional brain deficits and characteristic facial dysmorphism. In some patients, structural brain malformations, cardiac defects, genital anomalies, and cleft palate are observed. Early death occurs by the age of 3 years.<ref>PMID:19559399</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/FTO_HUMAN FTO_HUMAN]] Dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation. Has highest activity towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine. Has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine. Has no activity towards 1-methylguanine. Has no detectable activity towards double-stranded DNA. Requires molecular oxygen, alpha-ketoglutarate and iron. Contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis. Contributes to the regulation of body size and body fat accumulation.<ref>PMID:18775698</ref> <ref>PMID:20376003</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Gan, J]]
		+	[[Category: Huang, Y]]
		+	[[Category: Yang, C G]]
		+	[[Category: Jellyroll folding]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 09:59, 29 October 2014

OCA — Wed, 29 Oct 2014 09:59:26 GMT

←Older revision		Revision as of 09:59, 29 October 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Yang, C.-G., Huang, Y., Gan, J.		Authors: Yang, C.-G., Huang, Y., Gan, J.

	Description: Crystal structure of FTO bound to a selective inhibitor		Description: Crystal structure of FTO bound to a selective inhibitor

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

OCA — Wed, 18 Jun 2014 06:38:39 GMT

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

←Older revision

Revision as of 06:38, 18 June 2014

OCA: New page: '''Unreleased structure''' The entry 4qkn is ON HOLD Authors: Yang, C.-G., Huang, Y., Gan, J. Description: Crystal structure of FTO bound to a selective inhibitor

OCA — Wed, 18 Jun 2014 06:38:37 GMT

New page: '''Unreleased structure''' The entry 4qkn is ON HOLD Authors: Yang, C.-G., Huang, Y., Gan, J. Description: Crystal structure of FTO bound to a selective inhibitor

New page

'''Unreleased structure'''

The entry 4qkn is ON HOLD

Authors: Yang, C.-G., Huang, Y., Gan, J.

Description: Crystal structure of FTO bound to a selective inhibitor