5nxa - Revision history

OCA at 09:52, 15 November 2023

OCA — Wed, 15 Nov 2023 09:52:36 GMT

←Older revision		Revision as of 09:52, 15 November 2023
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	==Crystal structure of Neanderthal Adenylosuccinate Lyase (ADSL)in complex with its products AICAR and fumarate==		==Crystal structure of Neanderthal Adenylosuccinate Lyase (ADSL)in complex with its products AICAR and fumarate==
-	<StructureSection load='5nxa' size='340' side='right' caption='[[5nxa]], [[Resolution\|resolution]] 2.40Å' scene=''>	+	<StructureSection load='5nxa' size='340' side='right'caption='[[5nxa]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5nxa]] is a 8 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Feldhofer_1 Feldhofer 1~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NXA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5NXA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5nxa]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens_neanderthalensis Homo sapiens neanderthalensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NXA FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMZ:AMINOIMIDAZOLE+4-CARBOXAMIDE+RIBONUCLEOTIDE'>AMZ</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUM:FUMARIC+ACID'>FUM</scene>, <scene name='pdbligand=SSS:N-{[5-AMINO-1-(5-O-PHOSPHONO-BETA-D-ARABINOFURANOSYL)-1H-IMIDAZOL-4-YL]CARBONYL}-L-ASPARTIC+ACID'>SSS</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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ADSL, AMPS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=63221 Feldhofer 1])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMZ:AMINOIMIDAZOLE+4-CARBOXAMIDE+RIBONUCLEOTIDE'>AMZ</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUM:FUMARIC+ACID'>FUM</scene>, <scene name='pdbligand=SSS:N-{[5-AMINO-1-(5-O-PHOSPHONO-BETA-D-ARABINOFURANOSYL)-1H-IMIDAZOL-4-YL]CARBONYL}-L-ASPARTIC+ACID'>SSS</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenylosuccinate_lyase Adenylosuccinate lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.3.2.2 4.3.2.2] </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=5nxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nxa OCA], [https://pdbe.org/5nxa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nxa RCSB], [https://www.ebi.ac.uk/pdbsum/5nxa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nxa 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=5nxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nxa OCA], [~~http~~://pdbe.org/5nxa PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5nxa RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5nxa PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5nxa ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/A0A384E0N4_HOMNE A0A384E0N4_HOMNE] Catalyzes two non-sequential steps in de novo AMP synthesis: converts (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate (SAICAR) to fumarate plus 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide, and thereby also contributes to de novo IMP synthesis, and converts succinyladenosine monophosphate (SAMP) to AMP and fumarate.[ARBA:ARBA00002971]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 18:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5nxa" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5nxa" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Adenylosuccinate lyase 3D structures\|Adenylosuccinate lyase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Adenylosuccinate lyase~~]]	+	[[Category: Homo sapiens neanderthalensis]]
-	[[Category: ~~Feldhofer 1~~]]	+	[[Category: Large Structures]]
-	[[Category: Kapp, U]]	+	[[Category: Kapp U]]
-	~~[[Category: Laer, B Van~~]]	+	[[Category: Leonard G]]
-	[[Category: Leonard, G]]	+	[[Category: Mueller-Dieckmann C]]
-	[[Category: Mueller-Dieckmann, C]]	+	[[Category: Soler-Lopez M]]
-	[[Category: Soler-Lopez, M]]	+	[[Category: Van Laer B]]
-	[[Category: ~~Fumarase]]~~	+
-	~~[[Category: Lyase~~]]	+

OCA at 09:21, 30 January 2019

OCA — Wed, 30 Jan 2019 09:21:09 GMT

←Older revision		Revision as of 09:21, 30 January 2019
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	<StructureSection load='5nxa' size='340' side='right' caption='[[5nxa]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='5nxa' size='340' side='right' caption='[[5nxa]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5nxa]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NXA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NXA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5nxa]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Feldhofer_1 Feldhofer 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NXA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NXA FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMZ:AMINOIMIDAZOLE+4-CARBOXAMIDE+RIBONUCLEOTIDE'>AMZ</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUM:FUMARIC+ACID'>FUM</scene>, <scene name='pdbligand=SSS:N-{[5-AMINO-1-(5-O-PHOSPHONO-BETA-D-ARABINOFURANOSYL)-1H-IMIDAZOL-4-YL]CARBONYL}-L-ASPARTIC+ACID'>SSS</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMZ:AMINOIMIDAZOLE+4-CARBOXAMIDE+RIBONUCLEOTIDE'>AMZ</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUM:FUMARIC+ACID'>FUM</scene>, <scene name='pdbligand=SSS:N-{[5-AMINO-1-(5-O-PHOSPHONO-BETA-D-ARABINOFURANOSYL)-1H-IMIDAZOL-4-YL]CARBONYL}-L-ASPARTIC+ACID'>SSS</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ADSL, AMPS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=63221 Feldhofer 1])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenylosuccinate_lyase Adenylosuccinate lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.3.2.2 4.3.2.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenylosuccinate_lyase Adenylosuccinate lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.3.2.2 4.3.2.2] </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=5nxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nxa OCA], [http://pdbe.org/5nxa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nxa RCSB], [http://www.ebi.ac.uk/pdbsum/5nxa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nxa 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=5nxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nxa OCA], [http://pdbe.org/5nxa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nxa RCSB], [http://www.ebi.ac.uk/pdbsum/5nxa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nxa ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The availability of genomic data from extinct homini such as Neanderthals has caused a revolution in palaeontology allowing the identification of modern human-specific protein substitutions. Currently, little is known as to how these substitutions alter the proteins on a molecular level. Here, we investigate adenylosuccinate lyase, a conserved enzyme involved in purine metabolism for which several substitutions in the modern human protein (hADSL) have been described to affect intelligence and behaviour. During evolution, modern humans acquired a specific substitution (Ala429Val) in ADSL distinguishing it from the ancestral variant present in Neanderthals (nADSL). We show here that despite this conservative substitution being solvent exposed and located distant from the active site, there is a difference in thermal stability, but not enzymology or ligand binding between nADSL and hADSL. Substitutions near residue 429 which do not profoundly affect enzymology were previously reported to cause neurological symptoms in humans. This study also reveals that ADSL undergoes conformational changes during catalysis which, together with the crystal structure of a hitherto undetermined product bound conformation, explains the molecular origin of disease for several modern human ADSL mutants.
		+
		+	Molecular comparison of Neanderthal and Modern Human adenylosuccinate lyase.,Van Laer B, Kapp U, Soler-Lopez M, Moczulska K, Paabo S, Leonard G, Mueller-Dieckmann C Sci Rep. 2018 Dec 20;8(1):18008. doi: 10.1038/s41598-018-36195-5. PMID:30573755<ref>PMID:30573755</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5nxa" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Adenylosuccinate lyase]]		[[Category: Adenylosuccinate lyase]]
		+	[[Category: Feldhofer 1]]
	[[Category: Kapp, U]]		[[Category: Kapp, U]]
	[[Category: Laer, B Van]]		[[Category: Laer, B Van]]

OCA at 05:25, 30 May 2018

OCA — Wed, 30 May 2018 05:25:39 GMT

←Older revision		Revision as of 05:25, 30 May 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5nxa is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of Neanderthal Adenylosuccinate Lyase (ADSL)in complex with its products AICAR and fumarate==
-		+	<StructureSection load='5nxa' size='340' side='right' caption='[[5nxa]], [[Resolution\|resolution]] 2.40Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5nxa]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NXA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NXA FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMZ:AMINOIMIDAZOLE+4-CARBOXAMIDE+RIBONUCLEOTIDE'>AMZ</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUM:FUMARIC+ACID'>FUM</scene>, <scene name='pdbligand=SSS:N-{[5-AMINO-1-(5-O-PHOSPHONO-BETA-D-ARABINOFURANOSYL)-1H-IMIDAZOL-4-YL]CARBONYL}-L-ASPARTIC+ACID'>SSS</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenylosuccinate_lyase Adenylosuccinate lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.3.2.2 4.3.2.2] </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=5nxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nxa OCA], [http://pdbe.org/5nxa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nxa RCSB], [http://www.ebi.ac.uk/pdbsum/5nxa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nxa ProSAT]</span></td></tr>
		+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Adenylosuccinate lyase]]
		+	[[Category: Kapp, U]]
		+	[[Category: Laer, B Van]]
		+	[[Category: Leonard, G]]
		+	[[Category: Mueller-Dieckmann, C]]
		+	[[Category: Soler-Lopez, M]]
		+	[[Category: Fumarase]]
		+	[[Category: Lyase]]

OCA at 11:50, 27 September 2017

OCA — Wed, 27 Sep 2017 11:50:22 GMT

←Older revision		Revision as of 11:50, 27 September 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5nxa is ON HOLD	+	The entry 5nxa is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "5nxa" [edit=sysop:move=sysop]

OCA — Wed, 17 May 2017 12:23:19 GMT

Protected "5nxa" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:23, 17 May 2017

OCA: New page: '''Unreleased structure''' The entry 5nxa is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 17 May 2017 12:23:17 GMT

New page: '''Unreleased structure''' The entry 5nxa is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5nxa is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]