5vgy - Revision history

OCA at 13:48, 4 October 2023

2023-10-04T13:48:45Z

←Older revision		Revision as of 13:48, 4 October 2023
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	==Identification of a New Zinc Binding Chemotype by Fragment Screening==		==Identification of a New Zinc Binding Chemotype by Fragment Screening==
-	<StructureSection load='5vgy' size='340' side='right' caption='[[5vgy]], [[Resolution\|resolution]] 1.39Å' scene=''>	+	<StructureSection load='5vgy' size='340' side='right'caption='[[5vgy]], [[Resolution\|resolution]] 1.39Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vgy]] 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=5VGY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5VGY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vgy]] 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=5VGY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VGY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9AA:(5S)-5-[(2,4-dimethoxyphenyl)methyl]-5-hydroxy-2-sulfanylideneimidazolidin-4-one'>9AA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.39Å</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=9AA:(5S)-5-[(2,4-dimethoxyphenyl)methyl]-5-hydroxy-2-sulfanylideneimidazolidin-4-one'>9AA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=5vgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vgy OCA], [https://pdbe.org/5vgy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vgy RCSB], [https://www.ebi.ac.uk/pdbsum/5vgy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vgy 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=5vgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vgy OCA], [~~http~~://pdbe.org/5vgy PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5vgy RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5vgy PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5vgy 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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5vgy" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5vgy" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Carbonic anhydrase 3D structures\|Carbonic anhydrase 3D structures]]
		+	*[[Factor IX 3D structures\|Factor IX 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Carbonate dehydratase~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Human~~]]	+	[[Category: Large Structures]]
-	[[Category: Peat~~, T S]]~~	+	[[Category: Peat TS]]
-	~~[[Category: Carbonic anhydrase]]~~	+
-	~~[[Category: Fragment screening]]~~	+
-	~~[[Category: Lyase-lyase inhibitor complex~~]]	+

OCA at 14:41, 6 November 2017

2017-11-06T14:41:13Z

←Older revision		Revision as of 14:41, 6 November 2017
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	<StructureSection load='5vgy' size='340' side='right' caption='[[5vgy]], [[Resolution\|resolution]] 1.39Å' scene=''>		<StructureSection load='5vgy' size='340' side='right' caption='[[5vgy]], [[Resolution\|resolution]] 1.39Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vgy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VGY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VGY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vgy]] 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=5VGY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VGY FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9AA:(5S)-5-[(2,4-dimethoxyphenyl)methyl]-5-hydroxy-2-sulfanylideneimidazolidin-4-one'>9AA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=9AA:(5S)-5-[(2,4-dimethoxyphenyl)methyl]-5-hydroxy-2-sulfanylideneimidazolidin-4-one'>9AA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=5vgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vgy OCA], [http://pdbe.org/5vgy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vgy RCSB], [http://www.ebi.ac.uk/pdbsum/5vgy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vgy 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=5vgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vgy OCA], [http://pdbe.org/5vgy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vgy RCSB], [http://www.ebi.ac.uk/pdbsum/5vgy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vgy ProSAT]</span></td></tr>
Line 26:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Carbonate dehydratase]]		[[Category: Carbonate dehydratase]]
		+	[[Category: Human]]
	[[Category: Peat, T S]]		[[Category: Peat, T S]]
	[[Category: Carbonic anhydrase]]		[[Category: Carbonic anhydrase]]
	[[Category: Fragment screening]]		[[Category: Fragment screening]]
	[[Category: Lyase-lyase inhibitor complex]]		[[Category: Lyase-lyase inhibitor complex]]

OCA at 03:59, 30 August 2017

2017-08-30T03:59:26Z

←Older revision		Revision as of 03:59, 30 August 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5vgy is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Identification of a New Zinc Binding Chemotype by Fragment Screening==
		+	<StructureSection load='5vgy' size='340' side='right' caption='[[5vgy]], [[Resolution\|resolution]] 1.39Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5vgy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VGY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VGY FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9AA:(5S)-5-[(2,4-dimethoxyphenyl)methyl]-5-hydroxy-2-sulfanylideneimidazolidin-4-one'>9AA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=5vgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vgy OCA], [http://pdbe.org/5vgy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vgy RCSB], [http://www.ebi.ac.uk/pdbsum/5vgy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vgy 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 ==
		+	The discovery of a new zinc binding chemotype from screening a non-biased fragment library is reported. Using the orthogonal fragment screening methods of native state mass spectrometry and surface plasmon resonance a 3-unsubstituted-2,4-oxazolidinedione fragment was found to have low micromolar binding affinity to the zinc metalloenzyme carbonic anhydrase II (CA II). This affinity approached that of fragment sized primary benzene sulfonamides, the classical zinc binding group found in most CA II inhibitors. Protein X-ray crystallography established that 3-unsubstituted-2,4-oxazolidinediones bound to CA II via an interaction of the acidic ring nitrogen with the CA II active site zinc, as well as a hydrogen bond between the oxazolidinedione ring oxygen and the CA II protein backbone. Furthermore, 3-unsubstituted-2,4-oxazolidinediones appear to be a viable starting point for the development of an alternative class of CA inhibitor, wherein the medicinal chemistry pedigree of primary sulfonamides has dominated for several decades.

-	~~Authors:~~ Peat, T.S.	+	Identification of a New Zinc Binding Chemotype by Fragment Screening.,Chrysanthopoulos PK, Mujumdar P, Woods LA, Dolezal O, Ren B, Peat TS, Poulsen SA J Med Chem. 2017 Aug 17. doi: 10.1021/acs.jmedchem.7b00606. PMID:28817930<ref>PMID:28817930</ref>

-	~~Description: Identification of~~ a ~~New Zinc Binding Chemotype by Fragment Screening~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Peat, T.S]]	+	<div class="pdbe-citations 5vgy" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Carbonate dehydratase]]
		+	[[Category: Peat, T S]]
		+	[[Category: Carbonic anhydrase]]
		+	[[Category: Fragment screening]]
		+	[[Category: Lyase-lyase inhibitor complex]]

OCA at 11:31, 24 May 2017

2017-05-24T11:31:27Z

←Older revision		Revision as of 11:31, 24 May 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Peat, T.S.		Authors: Peat, T.S.

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

2017-04-19T11:26:10Z

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

←Older revision

Revision as of 11:26, 19 April 2017

OCA: New page: '''Unreleased structure''' The entry 5vgy is ON HOLD Authors: Peat, T.S. Description: Identification of a New Zinc Binding Chemotype by Fragment Screening [[Category: Unreleased Struct...

2017-04-19T11:26:08Z

New page: '''Unreleased structure''' The entry 5vgy is ON HOLD Authors: Peat, T.S. Description: Identification of a New Zinc Binding Chemotype by Fragment Screening [[Category: Unreleased Struct...

New page

'''Unreleased structure'''

The entry 5vgy is ON HOLD

Authors: Peat, T.S.

Description: Identification of a New Zinc Binding Chemotype by Fragment Screening
[[Category: Unreleased Structures]]
[[Category: Peat, T.S]]