6qaf - Revision history

OCA at 11:56, 24 January 2024

2024-01-24T11:56:44Z

←Older revision		Revision as of 11:56, 24 January 2024
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	<StructureSection load='6qaf' size='340' side='right'caption='[[6qaf]], [[Resolution\|resolution]] 1.61Å' scene=''>		<StructureSection load='6qaf' size='340' side='right'caption='[[6qaf]], [[Resolution\|resolution]] 1.61Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qaf]] is a 2 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=6QAF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6QAF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qaf]] is a 2 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=6QAF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QAF 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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=XC3:[(~{E})-3-[(3~{S},4~{R})-4-azanyl-1-[(2~{S})-2-azanylpropanoyl]-4-carboxy-pyrrolidin-3-yl]prop-1-enyl]-tris(oxidanyl)boranium'>XC3</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]] 1.61Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6q92\|6q92]], [[6q9p\|6q9p]]</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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=XC3:[(~{E})-3-[(3~{S},4~{R})-4-azanyl-1-[(2~{S})-2-azanylpropanoyl]-4-carboxy-pyrrolidin-3-yl]prop-1-enyl]-tris(oxidanyl)boranium'>XC3</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ARG1 ([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=6qaf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qaf OCA], [https://pdbe.org/6qaf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qaf RCSB], [https://www.ebi.ac.uk/pdbsum/6qaf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qaf ProSAT]</span></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Arginase Arginase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.1 3.5.3.1] </span></td></tr>	+
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6qaf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qaf OCA], [~~http~~://pdbe.org/6qaf PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6qaf RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6qaf PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6qaf ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/ARGI1_HUMAN ARGI1_HUMAN]] Defects in ARG1 are the cause of argininemia (ARGIN) [MIM:[~~http~~://omim.org/entry/207800 207800]]; also known as hyperargininemia. Argininemia is a rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, mental retardation, hypotonia, ataxia, progressive spastic quadriplegia.<ref>PMID:1463019</ref> <ref>PMID:7649538</ref>	+	[https://www.uniprot.org/uniprot/ARGI1_HUMAN ARGI1_HUMAN] Defects in ARG1 are the cause of argininemia (ARGIN) [MIM:[https://omim.org/entry/207800 207800]; also known as hyperargininemia. Argininemia is a rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, mental retardation, hypotonia, ataxia, progressive spastic quadriplegia.<ref>PMID:1463019</ref> <ref>PMID:7649538</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/ARGI1_HUMAN ARGI1_HUMAN]
	<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: ~~Arginase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Grobben, Y]]	+	[[Category: Grobben Y]]
-	[[Category: Tabak~~, W W.A~~]]	+	[[Category: Tabak WWA]]
-	[[Category: Uitdehaag~~, J C.M~~]]	+	[[Category: Uitdehaag JCM]]
-	[[Category: Zaman~~, G J.R]]~~	+	[[Category: Zaman GJR]]
-	~~[[Category: Arignase inhibitor]]~~	+
-	~~[[Category: Borate]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Manganese cluster]]~~	+
-	~~[[Category: Ph-dependent~~]]	+

OCA at 11:23, 22 July 2020

2020-07-22T11:23:39Z

←Older revision		Revision as of 11:23, 22 July 2020
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	<StructureSection load='6qaf' size='340' side='right'caption='[[6qaf]], [[Resolution\|resolution]] 1.61Å' scene=''>		<StructureSection load='6qaf' size='340' side='right'caption='[[6qaf]], [[Resolution\|resolution]] 1.61Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qaf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QAF OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6QAF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qaf]] is a 2 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=6QAF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6QAF 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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=XC3:[(~{E})-3-[(3~{S},4~{R})-4-azanyl-1-[(2~{S})-2-azanylpropanoyl]-4-carboxy-pyrrolidin-3-yl]prop-1-enyl]-tris(oxidanyl)boranium'>XC3</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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=XC3:[(~{E})-3-[(3~{S},4~{R})-4-azanyl-1-[(2~{S})-2-azanylpropanoyl]-4-carboxy-pyrrolidin-3-yl]prop-1-enyl]-tris(oxidanyl)boranium'>XC3</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6q92\|6q92]], [[6q9p\|6q9p]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6q92\|6q92]], [[6q9p\|6q9p]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ARG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Arginase Arginase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.1 3.5.3.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Arginase Arginase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.1 3.5.3.1] </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=6qaf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qaf OCA], [http://pdbe.org/6qaf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qaf RCSB], [http://www.ebi.ac.uk/pdbsum/6qaf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qaf ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6qaf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qaf OCA], [http://pdbe.org/6qaf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qaf RCSB], [http://www.ebi.ac.uk/pdbsum/6qaf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qaf ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/ARGI1_HUMAN ARGI1_HUMAN]] Defects in ARG1 are the cause of argininemia (ARGIN) [MIM:[http://omim.org/entry/207800 207800]]; also known as hyperargininemia. Argininemia is a rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, mental retardation, hypotonia, ataxia, progressive spastic quadriplegia.<ref>PMID:1463019</ref> <ref>PMID:7649538</ref>		[[http://www.uniprot.org/uniprot/ARGI1_HUMAN ARGI1_HUMAN]] Defects in ARG1 are the cause of argininemia (ARGIN) [MIM:[http://omim.org/entry/207800 207800]]; also known as hyperargininemia. Argininemia is a rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, mental retardation, hypotonia, ataxia, progressive spastic quadriplegia.<ref>PMID:1463019</ref> <ref>PMID:7649538</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Arginase-1 is a manganese-dependent metalloenzyme that catalyzes the hydrolysis of L-arginine into L-ornithine and urea. Arginase-1 is abundantly expressed by tumor-infiltrating myeloid cells that promote tumor immunosuppression, which is relieved by inhibition of Arginase-1. We have characterized the potencies of the Arginase-1 reference inhibitors (2S)-2-amino-6-boronohexanoic acid (ABH) and N (omega)-hydroxy-nor-L-arginine (nor-NOHA), and studied their pH-dependence and binding kinetics. To gain a better understanding of the structural changes underlying the high pH optimum of Arginase-1 and its pH-dependent inhibition, we determined the crystal structure of the human Arginase-1/ABH complex at pH 7.0 and 9.0. These structures revealed that at increased pH, the manganese cluster assumes a more symmetrical coordination structure, which presumably contributes to its increase in catalytic activity. Furthermore, we show that binding of ABH involves the presence of a sodium ion close to the manganese cluster. We also studied the investigational new drug CB-1158 (INCB001158). This inhibitor has a low-nanomolar potency at pH 7.4 and increases the thermal stability of Arginase-1 more than ABH and nor-NOHA. Moreover, CB-1158 displays slow association and dissociation kinetics at both pH 9.5 and 7.4, as indicated by surface plasmon resonance. The potent character of CB-1158 is presumably due to its increased rigidity compared to ABH as well as the formation of an additional hydrogen-bond network as observed by resolution of the Arginase-1/CB-1158 crystal structure.
		+
		+	Structural insights into human Arginase-1 pH dependence and its inhibition by the small molecule inhibitor CB-1158.,Grobben Y, Uitdehaag JCM, Willemsen-Seegers N, Tabak WWA, de Man J, Buijsman RC, Zaman GJR J Struct Biol X. 2019 Nov 26;4:100014. doi: 10.1016/j.yjsbx.2019.100014., eCollection 2020. PMID:32647818<ref>PMID:32647818</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6qaf" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Arginase 3D structures\|Arginase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 16:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Arginase]]		[[Category: Arginase]]
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Grobben, Y]]		[[Category: Grobben, Y]]

OCA at 15:14, 11 December 2019

2019-12-11T15:14:21Z

←Older revision		Revision as of 15:14, 11 December 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6qaf is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of human Arginase-1 at pH 9.0 in complex with CB-1158/INCB001158==
-		+	<StructureSection load='6qaf' size='340' side='right'caption='[[6qaf]], [[Resolution\|resolution]] 1.61Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6qaf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QAF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QAF FirstGlance]. <br>
-	~~Description~~:	+	</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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=XC3:[(~{E})-3-[(3~{S},4~{R})-4-azanyl-1-[(2~{S})-2-azanylpropanoyl]-4-carboxy-pyrrolidin-3-yl]prop-1-enyl]-tris(oxidanyl)boranium'>XC3</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6q92\|6q92]], [[6q9p\|6q9p]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Arginase Arginase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.1 3.5.3.1] </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=6qaf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qaf OCA], [http://pdbe.org/6qaf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qaf RCSB], [http://www.ebi.ac.uk/pdbsum/6qaf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qaf ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/ARGI1_HUMAN ARGI1_HUMAN]] Defects in ARG1 are the cause of argininemia (ARGIN) [MIM:[http://omim.org/entry/207800 207800]]; also known as hyperargininemia. Argininemia is a rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, mental retardation, hypotonia, ataxia, progressive spastic quadriplegia.<ref>PMID:1463019</ref> <ref>PMID:7649538</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Arginase]]
		+	[[Category: Large Structures]]
		+	[[Category: Grobben, Y]]
		+	[[Category: Tabak, W W.A]]
		+	[[Category: Uitdehaag, J C.M]]
		+	[[Category: Zaman, G J.R]]
		+	[[Category: Arignase inhibitor]]
		+	[[Category: Borate]]
		+	[[Category: Hydrolase]]
		+	[[Category: Manganese cluster]]
		+	[[Category: Ph-dependent]]

OCA at 06:22, 4 December 2019

2019-12-04T06:22:09Z

←Older revision		Revision as of 06:22, 4 December 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6qaf is ON HOLD	+	The entry 6qaf is ON HOLD until Paper Publication

	Authors:		Authors:

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

2018-12-26T07:02:53Z

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

←Older revision

Revision as of 07:02, 26 December 2018

OCA: New page: '''Unreleased structure''' The entry 6qaf is ON HOLD Authors: Description: Category: Unreleased Structures

2018-12-26T07:02:52Z

New page: '''Unreleased structure''' The entry 6qaf is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6qaf is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]