6aej - Revision history

OCA at 09:28, 22 November 2023

OCA — Wed, 22 Nov 2023 09:28:16 GMT

←Older revision		Revision as of 09:28, 22 November 2023
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	<StructureSection load='6aej' size='340' side='right'caption='[[6aej]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='6aej' size='340' side='right'caption='[[6aej]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6aej]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AEJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6AEJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6aej]] 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=6AEJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AEJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7YC:(E)-3-[3-nitro-4,5-bis(oxidanyl)phenyl]-2-(1,3-oxazinan-3-ylcarbonyl)prop-2-enenitrile'>7YC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.8Å</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=6aej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aej OCA], [~~http~~://pdbe.org/6aej PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6aej RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6aej PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6aej ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7YC:(E)-3-[3-nitro-4,5-bis(oxidanyl)phenyl]-2-(1,3-oxazinan-3-ylcarbonyl)prop-2-enenitrile'>7YC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6aej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aej OCA], [https://pdbe.org/6aej PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6aej RCSB], [https://www.ebi.ac.uk/pdbsum/6aej PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6aej 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 ==
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	</div>		</div>
	<div class="pdbe-citations 6aej" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6aej" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dioxygenase 3D structures\|Dioxygenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cao, R]]	+	[[Category: Cao R]]
-	[[Category: Huang, N]]	+	[[Category: Huang N]]
-	[[Category: Peng, S]]	+	[[Category: Peng S]]
-	[[Category: Wang, Y]]	+	[[Category: Wang Y]]
-	[[Category: Zhang, W]]	+	[[Category: Zhang W]]
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 05:50, 19 June 2019

OCA — Wed, 19 Jun 2019 05:50:06 GMT

←Older revision		Revision as of 05:50, 19 June 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6aej is ~~ON HOLD~~ ~~until Aug 05 2020~~	+	==Crystal structure of human FTO in complex with small-molecule inhibitors==
		+	<StructureSection load='6aej' size='340' side='right'caption='[[6aej]], [[Resolution\|resolution]] 2.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6aej]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AEJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AEJ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7YC:(E)-3-[3-nitro-4,5-bis(oxidanyl)phenyl]-2-(1,3-oxazinan-3-ylcarbonyl)prop-2-enenitrile'>7YC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6aej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aej OCA], [http://pdbe.org/6aej PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aej RCSB], [http://www.ebi.ac.uk/pdbsum/6aej PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aej ProSAT]</span></td></tr>
		+	</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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Recent studies have established the involvement of the fat mass and obesity-associated gene (FTO) in metabolic disorders such as obesity and diabetes. However, the precise molecular mechanism by which FTO regulates metabolism remains unknown. Here, we used a structure-based virtual screening of U.S. Food and Drug Administration-approved drugs to identify entacapone as a potential FTO inhibitor. Using structural and biochemical studies, we showed that entacapone directly bound to FTO and inhibited FTO activity in vitro. Furthermore, entacapone administration reduced body weight and lowered fasting blood glucose concentrations in diet-induced obese mice. We identified the transcription factor forkhead box protein O1 (FOXO1) mRNA as a direct substrate of FTO, and demonstrated that entacapone elicited its effects on gluconeogenesis in the liver and thermogenesis in adipose tissues in mice by acting on an FTO-FOXO1 regulatory axis.

-	~~Authors: Wang~~, Y., ~~Cao~~, R., ~~Peng~~, S., ~~Zhang~~, W., Huang, N.	+	Identification of entacapone as a chemical inhibitor of FTO mediating metabolic regulation through FOXO1.,Peng S, Xiao W, Ju D, Sun B, Hou N, Liu Q, Wang Y, Zhao H, Gao C, Zhang S, Cao R, Li P, Huang H, Ma Y, Wang Y, Lai W, Ma Z, Zhang W, Huang S, Wang H, Zhang Z, Zhao L, Cai T, Zhao YL, Wang F, Nie Y, Zhi G, Yang YG, Zhang EE, Huang N Sci Transl Med. 2019 Apr 17;11(488). pii: 11/488/eaau7116. doi:, 10.1126/scitranslmed.aau7116. PMID:30996080<ref>PMID:30996080</ref>

-	~~Description: Crystal structure~~ of ~~human FTO in complex with small~~-~~molecule inhibitors~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6aej" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Cao, R]]		[[Category: Cao, R]]
	[[Category: Huang, N]]		[[Category: Huang, N]]
-	[[Category: Zhang, W]]
	[[Category: Peng, S]]		[[Category: Peng, S]]
	[[Category: Wang, Y]]		[[Category: Wang, Y]]
		+	[[Category: Zhang, W]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 04:46, 2 January 2019

OCA — Wed, 02 Jan 2019 04:46:39 GMT

←Older revision		Revision as of 04:46, 2 January 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6aej is ON HOLD	+	The entry 6aej is ON HOLD until Aug 05 2020

	Authors: Wang, Y., Cao, R., Peng, S., Zhang, W., Huang, N.		Authors: Wang, Y., Cao, R., Peng, S., Zhang, W., Huang, N.

OCA: Protected "6aej" [edit=sysop:move=sysop]

OCA — Wed, 15 Aug 2018 14:38:11 GMT

Protected "6aej" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:38, 15 August 2018

OCA: New page: '''Unreleased structure''' The entry 6aej is ON HOLD Authors: Wang, Y., Cao, R., Peng, S., Zhang, W., Huang, N. Description: Crystal structure of human FTO in complex with small-molecu...

OCA — Wed, 15 Aug 2018 14:38:09 GMT

New page: '''Unreleased structure''' The entry 6aej is ON HOLD Authors: Wang, Y., Cao, R., Peng, S., Zhang, W., Huang, N. Description: Crystal structure of human FTO in complex with small-molecu...

New page

'''Unreleased structure'''

The entry 6aej is ON HOLD

Authors: Wang, Y., Cao, R., Peng, S., Zhang, W., Huang, N.

Description: Crystal structure of human FTO in complex with small-molecule inhibitors
[[Category: Unreleased Structures]]
[[Category: Cao, R]]
[[Category: Huang, N]]
[[Category: Zhang, W]]
[[Category: Peng, S]]
[[Category: Wang, Y]]