5wgp - Revision history

OCA at 14:15, 13 March 2024

2024-03-13T14:15:53Z

←Older revision		Revision as of 14:15, 13 March 2024
Line 1:		Line 1:

	==Human Carbonic Anhydrase IX-mimic complexed with AceK==		==Human Carbonic Anhydrase IX-mimic complexed with AceK==
-	<StructureSection load='5wgp' size='340' side='right' caption='[[5wgp]], [[Resolution\|resolution]] 1.53Å' scene=''>	+	<StructureSection load='5wgp' size='340' side='right'caption='[[5wgp]], [[Resolution\|resolution]] 1.53Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wgp]] 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=5WGP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5WGP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wgp]] 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=5WGP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WGP FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name~~=~~'pdbligand=AUD:Acesulfame'>AUD</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]] 1.53Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>CA2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9606 HUMAN])</td~~><~~/tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AUD:Acesulfame'>AUD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>~~[http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1]~~ </~~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=5wgp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wgp OCA], [https://pdbe.org/5wgp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wgp RCSB], [https://www.ebi.ac.uk/pdbsum/5wgp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wgp 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=5wgp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wgp OCA], [~~http~~://pdbe.org/5wgp PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5wgp RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5wgp PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5wgp ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN]] Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:[~~http~~://omim.org/entry/259730 259730]]; also known as osteopetrosis with renal tubular acidosis, carbonic anhydrase II deficiency syndrome, Guibaud-Vainsel syndrome or marble brain disease. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Autosomal recessive osteopetrosis is usually associated with normal or elevated amount of non-functional osteoclasts. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation.<ref>PMID:1928091</ref> <ref>PMID:1542674</ref> <ref>PMID:8834238</ref> <ref>PMID:9143915</ref> <ref>PMID:15300855</ref>	+	[https://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN] Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:[https://omim.org/entry/259730 259730]; also known as osteopetrosis with renal tubular acidosis, carbonic anhydrase II deficiency syndrome, Guibaud-Vainsel syndrome or marble brain disease. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Autosomal recessive osteopetrosis is usually associated with normal or elevated amount of non-functional osteoclasts. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation.<ref>PMID:1928091</ref> <ref>PMID:1542674</ref> <ref>PMID:8834238</ref> <ref>PMID:9143915</ref> <ref>PMID:15300855</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN]] Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye.<ref>PMID:10550681</ref> <ref>PMID:11831900</ref>	+	[https://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN] Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye.<ref>PMID:10550681</ref> <ref>PMID:11831900</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Human carbonic anhydrase IX (CA IX) is upregulated in neoplastic tissues; as such, it is studied as a drug target for anticancer chemotherapy. Inhibition of CA IX has been shown to be therapeutically favorable in terms of reducing tumor growth. Previously, saccharin, a commonly used artificial sweetener, has been observed to selectively inhibit CA IX over other CA isoforms. In this study, X-ray crystallography showed acesulfame potassium (Ace K) binding directly to the catalytic zinc in CA IX (mimic) and through a bridging water in CA II. This modulation in binding is reflected in the binding constants, with Ace K inhibiting CA IX but not other CA isoforms. Hence, this study establishes the potential of Ace K (an FDA approved food additive) as a lead compound in the design and development of CA IX specific inhibitors.	+

-	"Seriously Sweet": Acesulfame K Exhibits Selective Inhibition Using Alternative Binding Modes in Carbonic Anhydrase Isoforms.,Murray AB, Lomelino CL, Supuran CT, McKenna R J Med Chem. 2018 Jan 5. doi: 10.1021/acs.jmedchem.7b01470. PMID:29266943<ref>PMID:29266943</ref>	+	==See Also==
-		+	*[[Carbonic anhydrase 3D structures\|Carbonic anhydrase 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class~~=~~"pdbe-citations 5wgp" style~~=~~"background-color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Carbonate dehydratase~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Human~~]]	+	[[Category: Large Structures]]
-	[[Category: Lomelino~~, C L~~]]	+	[[Category: Lomelino CL]]
-	[[Category: McKenna, R]]	+	[[Category: McKenna R]]
-	[[Category: Murray~~, A B~~]]	+	[[Category: Murray AB]]
-	[[Category: Supuran~~, C T]]~~	+	[[Category: Supuran CT]]
-	~~[[Category: Acesulfame]]~~	+
-	~~[[Category: Carbonic anhydrase]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Lyase~~]]	+

OCA at 08:22, 22 February 2018

2018-02-22T08:22:41Z

←Older revision		Revision as of 08:22, 22 February 2018
Line 3:		Line 3:
	<StructureSection load='5wgp' size='340' side='right' caption='[[5wgp]], [[Resolution\|resolution]] 1.53Å' scene=''>		<StructureSection load='5wgp' size='340' side='right' caption='[[5wgp]], [[Resolution\|resolution]] 1.53Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wgp]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WGP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WGP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wgp]] 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=5WGP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WGP FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AUD:Acesulfame'>AUD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AUD:Acesulfame'>AUD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CA2 ([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/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] </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=5wgp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wgp OCA], [http://pdbe.org/5wgp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wgp RCSB], [http://www.ebi.ac.uk/pdbsum/5wgp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wgp 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=5wgp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wgp OCA], [http://pdbe.org/5wgp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wgp RCSB], [http://www.ebi.ac.uk/pdbsum/5wgp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wgp ProSAT]</span></td></tr>
Line 26:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Carbonate dehydratase]]		[[Category: Carbonate dehydratase]]
		+	[[Category: Human]]
	[[Category: Lomelino, C L]]		[[Category: Lomelino, C L]]
	[[Category: McKenna, R]]		[[Category: McKenna, R]]

OCA at 06:14, 7 February 2018

2018-02-07T06:14:19Z

←Older revision		Revision as of 06:14, 7 February 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5wgp is ~~ON HOLD~~	+	==Human Carbonic Anhydrase IX-mimic complexed with AceK==
		+	<StructureSection load='5wgp' size='340' side='right' caption='[[5wgp]], [[Resolution\|resolution]] 1.53Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5wgp]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WGP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WGP FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AUD:Acesulfame'>AUD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] </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=5wgp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wgp OCA], [http://pdbe.org/5wgp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wgp RCSB], [http://www.ebi.ac.uk/pdbsum/5wgp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wgp ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN]] Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:[http://omim.org/entry/259730 259730]]; also known as osteopetrosis with renal tubular acidosis, carbonic anhydrase II deficiency syndrome, Guibaud-Vainsel syndrome or marble brain disease. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Autosomal recessive osteopetrosis is usually associated with normal or elevated amount of non-functional osteoclasts. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation.<ref>PMID:1928091</ref> <ref>PMID:1542674</ref> <ref>PMID:8834238</ref> <ref>PMID:9143915</ref> <ref>PMID:15300855</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN]] Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye.<ref>PMID:10550681</ref> <ref>PMID:11831900</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Human carbonic anhydrase IX (CA IX) is upregulated in neoplastic tissues; as such, it is studied as a drug target for anticancer chemotherapy. Inhibition of CA IX has been shown to be therapeutically favorable in terms of reducing tumor growth. Previously, saccharin, a commonly used artificial sweetener, has been observed to selectively inhibit CA IX over other CA isoforms. In this study, X-ray crystallography showed acesulfame potassium (Ace K) binding directly to the catalytic zinc in CA IX (mimic) and through a bridging water in CA II. This modulation in binding is reflected in the binding constants, with Ace K inhibiting CA IX but not other CA isoforms. Hence, this study establishes the potential of Ace K (an FDA approved food additive) as a lead compound in the design and development of CA IX specific inhibitors.

-	~~Authors~~:	+	"Seriously Sweet": Acesulfame K Exhibits Selective Inhibition Using Alternative Binding Modes in Carbonic Anhydrase Isoforms.,Murray AB, Lomelino CL, Supuran CT, McKenna R J Med Chem. 2018 Jan 5. doi: 10.1021/acs.jmedchem.7b01470. PMID:29266943<ref>PMID:29266943</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5wgp" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Carbonate dehydratase]]
		+	[[Category: Lomelino, C L]]
		+	[[Category: McKenna, R]]
		+	[[Category: Murray, A B]]
		+	[[Category: Supuran, C T]]
		+	[[Category: Acesulfame]]
		+	[[Category: Carbonic anhydrase]]
		+	[[Category: Inhibitor]]
		+	[[Category: Lyase]]

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

2017-09-27T14:48:46Z

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

←Older revision

Revision as of 14:48, 27 September 2017

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

2017-09-27T14:48:45Z

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

New page

'''Unreleased structure'''

The entry 5wgp is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]