6q6q - Revision history

OCA at 11:54, 24 January 2024

OCA — Wed, 24 Jan 2024 11:54:10 GMT

←Older revision		Revision as of 11:54, 24 January 2024
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	<StructureSection load='6q6q' size='340' side='right'caption='[[6q6q]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='6q6q' size='340' side='right'caption='[[6q6q]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6q6q]] 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=6Q6Q OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6Q6Q FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6q6q]] 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=6Q6Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Q6Q FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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]] 3.1000378Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4uhx\|4uhx]], [[4uhw\|4uhw]], [[5epg\|5epg]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AOX1, AO ([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=6q6q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q6q OCA], [https://pdbe.org/6q6q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6q6q RCSB], [https://www.ebi.ac.uk/pdbsum/6q6q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6q6q 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=6q6q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q6q OCA], [~~http~~://pdbe.org/6q6q PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6q6q RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6q6q PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6q6q ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/AOXA_HUMAN AOXA_HUMAN]] Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyzing the oxidation step from 6-deoxypenciclovir to penciclovir, which is a potent antiviral agent. Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. Also may catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor. May play a role in adipogenesis.<ref>PMID:20444863</ref> <ref>PMID:22031625</ref> <ref>PMID:22279051</ref> <ref>PMID:22522748</ref> <ref>PMID:22996261</ref> <ref>PMID:23857892</ref> <ref>PMID:7786031</ref> <ref>PMID:9224775</ref>	+	[https://www.uniprot.org/uniprot/AOXA_HUMAN AOXA_HUMAN] Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyzing the oxidation step from 6-deoxypenciclovir to penciclovir, which is a potent antiviral agent. Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. Also may catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor. May play a role in adipogenesis.<ref>PMID:20444863</ref> <ref>PMID:22031625</ref> <ref>PMID:22279051</ref> <ref>PMID:22522748</ref> <ref>PMID:22996261</ref> <ref>PMID:23857892</ref> <ref>PMID:7786031</ref> <ref>PMID:9224775</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Coelho, C]]	+	[[Category: Coelho C]]
-	[[Category: Mota, C]]	+	[[Category: Mota C]]
-	[[Category: Romao~~, M J~~]]	+	[[Category: Romao MJ]]
-	[[Category: Santos-Silva, T]]	+	[[Category: Santos-Silva T]]
-	~~[[Category: Moco-free form]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Single-nucleotide polymorphism~~]]	+

OCA at 13:44, 10 May 2019

OCA — Fri, 10 May 2019 13:44:29 GMT

←Older revision		Revision as of 13:44, 10 May 2019
Line 3:		Line 3:
	<StructureSection load='6q6q' size='340' side='right'caption='[[6q6q]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='6q6q' size='340' side='right'caption='[[6q6q]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6q6q]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q6Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6Q6Q FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6q6q]] 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=6Q6Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6Q6Q FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4uhx\|4uhx]], [[4uhw\|4uhw]], [[5epg\|5epg]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4uhx\|4uhx]], [[4uhw\|4uhw]], [[5epg\|5epg]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AOX1, AO ([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=6q6q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q6q OCA], [http://pdbe.org/6q6q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q6q RCSB], [http://www.ebi.ac.uk/pdbsum/6q6q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q6q 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=6q6q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q6q OCA], [http://pdbe.org/6q6q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q6q RCSB], [http://www.ebi.ac.uk/pdbsum/6q6q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q6q ProSAT]</span></td></tr>
	</table>		</table>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Coelho, C]]		[[Category: Coelho, C]]

OCA at 08:56, 1 May 2019

OCA — Wed, 01 May 2019 08:56:43 GMT

←Older revision		Revision as of 08:56, 1 May 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6q6q is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Human aldehyde oxidase SNP G1269R==
		+	<StructureSection load='6q6q' size='340' side='right'caption='[[6q6q]], [[Resolution\|resolution]] 3.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6q6q]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q6Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6Q6Q FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4uhx\|4uhx]], [[4uhw\|4uhw]], [[5epg\|5epg]]</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=6q6q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q6q OCA], [http://pdbe.org/6q6q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q6q RCSB], [http://www.ebi.ac.uk/pdbsum/6q6q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q6q ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/AOXA_HUMAN AOXA_HUMAN]] Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyzing the oxidation step from 6-deoxypenciclovir to penciclovir, which is a potent antiviral agent. Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. Also may catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor. May play a role in adipogenesis.<ref>PMID:20444863</ref> <ref>PMID:22031625</ref> <ref>PMID:22279051</ref> <ref>PMID:22522748</ref> <ref>PMID:22996261</ref> <ref>PMID:23857892</ref> <ref>PMID:7786031</ref> <ref>PMID:9224775</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Human aldehyde oxidase (hAOX1) is a molybdenum enzyme with high toxicological importance, but its physiological role is still unknown. hAOX1 metabolizes different classes of xenobiotics and is one of the main drug-metabolizing enzymes in the liver, along with cytochrome P450. hAOX1 oxidizes and inactivates a large number of drug molecules and has been responsible for the failure of several phase I clinical trials. The interindividual variability of drug-metabolizing enzymes caused by single nucleotide polymorphisms (SNPs) is highly relevant in pharmaceutical treatments. In this study, we present the crystal structure of the inactive variant G1269R, revealing the first structure of a molybdenum cofactor (Moco)-free form of hAOX1. These data allowed to model, for the first time, the flexible Gate 1 that controls access to the active site. Furthermore, we inspected the thermostability of wild-type hAOX1 and hAOX1 with various SNPs (L438V, R1231H, G1269R or S1271L) by CD spectroscopy and ThermoFAD, revealing that amino acid exchanges close to the Moco site can impact protein stability up to 10 degrees C. These results correlated with biochemical and structural data and enhance our understanding of hAOX1 and the effect of SNPs in the gene encoding this enzyme in the human population. ENZYMES: Aldehyde oxidase (EC1.2.3.1); xanthine dehydrogenase (EC1.17.1.4); xanthine oxidase (EC1.1.3.2). DATABASES: Structural data are available in the Protein Data Bank under the accession number 6Q6Q.

-	~~Authors~~: ~~Mota~~, C., ~~Coelho~~, C., Santos-Silva, T~~., Romao~~, M.J.	+	Human aldehyde oxidase (hAOX1): structure determination of the Moco-free form of the natural variant G1269R and biophysical studies of single nucleotide polymorphisms.,Mota C, Esmaeeli M, Coelho C, Santos-Silva T, Wolff M, Foti A, Leimkuhler S, Romao MJ FEBS Open Bio. 2019 May;9(5):925-934. doi: 10.1002/2211-5463.12617. Epub 2019 Apr, 15. PMID:30985987<ref>PMID:30985987</ref>

-	~~Description: Human aldehyde oxidase SNP G1269R~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Mota, C~~]]	+	<div class="pdbe-citations 6q6q" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Coelho, C]]		[[Category: Coelho, C]]
		+	[[Category: Mota, C]]
		+	[[Category: Romao, M J]]
	[[Category: Santos-Silva, T]]		[[Category: Santos-Silva, T]]
-	[[Category: ~~Romao, M.J~~]]	+	[[Category: Moco-free form]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Single-nucleotide polymorphism]]

OCA: Protected "6q6q" [edit=sysop:move=sysop]

OCA — Wed, 19 Dec 2018 06:47:39 GMT

Protected "6q6q" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:47, 19 December 2018

OCA: New page: '''Unreleased structure''' The entry 6q6q is ON HOLD until Paper Publication Authors: Mota, C., Coelho, C., Santos-Silva, T., Romao, M.J. Description: Human aldehyde oxidase SNP G1269R...

OCA — Wed, 19 Dec 2018 06:47:37 GMT

New page: '''Unreleased structure''' The entry 6q6q is ON HOLD until Paper Publication Authors: Mota, C., Coelho, C., Santos-Silva, T., Romao, M.J. Description: Human aldehyde oxidase SNP G1269R...

New page

'''Unreleased structure'''

The entry 6q6q is ON HOLD until Paper Publication

Authors: Mota, C., Coelho, C., Santos-Silva, T., Romao, M.J.

Description: Human aldehyde oxidase SNP G1269R
[[Category: Unreleased Structures]]
[[Category: Mota, C]]
[[Category: Coelho, C]]
[[Category: Santos-Silva, T]]
[[Category: Romao, M.J]]