5txy - Revision history

OCA at 14:24, 6 March 2024

OCA — Wed, 06 Mar 2024 14:24:05 GMT

←Older revision		Revision as of 14:24, 6 March 2024
Line 1:		Line 1:

	==Identification of a New Zinc Binding Chemotype of by Fragment Screening on human carbonic anhydrase==		==Identification of a New Zinc Binding Chemotype of by Fragment Screening on human carbonic anhydrase==
-	<StructureSection load='5txy' size='340' side='right' caption='[[5txy]], [[Resolution\|resolution]] 1.21Å' scene=''>	+	<StructureSection load='5txy' size='340' side='right'caption='[[5txy]], [[Resolution\|resolution]] 1.21Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5txy]] 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=5TXY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5TXY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5txy]] 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=5TXY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TXY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7Q1:(5R)-5-phenyl-1,3-oxazolidine-2,4-dione'>7Q1</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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]] 1.206Å</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=7Q1:(5R)-5-phenyl-1,3-oxazolidine-2,4-dione'>7Q1</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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=5txy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5txy OCA], [https://pdbe.org/5txy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5txy RCSB], [https://www.ebi.ac.uk/pdbsum/5txy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5txy 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=5txy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5txy OCA], [~~http~~://pdbe.org/5txy PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5txy RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5txy PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5txy 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 ==~~	+
-	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.	+

-	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>	+	==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 5txy" 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: Peat~~, T S~~]]	+	[[Category: Peat TS]]
-	[[Category: Poulsen, S A]]	+	[[Category: Poulsen S-A]]
-	[[Category: Ren, B]]	+	[[Category: Ren B]]
-	~~[[Category: Crystal]]~~	+
-	~~[[Category: Crystallization]]~~	+
-	~~[[Category: Human carbonic anhydrase]]~~	+
-	~~[[Category: Lyase]]~~	+
-	~~[[Category: Zinc binding chemotype~~]]	+

OCA at 14:28, 6 November 2017

OCA — Mon, 06 Nov 2017 14:28:31 GMT

←Older revision		Revision as of 14:28, 6 November 2017
Line 3:		Line 3:
	<StructureSection load='5txy' size='340' side='right' caption='[[5txy]], [[Resolution\|resolution]] 1.21Å' scene=''>		<StructureSection load='5txy' size='340' side='right' caption='[[5txy]], [[Resolution\|resolution]] 1.21Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5txy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TXY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TXY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5txy]] 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=5TXY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TXY FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7Q1:(5R)-5-phenyl-1,3-oxazolidine-2,4-dione'>7Q1</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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=7Q1:(5R)-5-phenyl-1,3-oxazolidine-2,4-dione'>7Q1</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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=5txy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5txy OCA], [http://pdbe.org/5txy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5txy RCSB], [http://www.ebi.ac.uk/pdbsum/5txy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5txy 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=5txy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5txy OCA], [http://pdbe.org/5txy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5txy RCSB], [http://www.ebi.ac.uk/pdbsum/5txy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5txy 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: Poulsen, S A]]		[[Category: Poulsen, S A]]

OCA at 04:00, 30 August 2017

OCA — Wed, 30 Aug 2017 04:00:11 GMT

←Older revision		Revision as of 04:00, 30 August 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5txy is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Identification of a New Zinc Binding Chemotype of by Fragment Screening on human carbonic anhydrase==
		+	<StructureSection load='5txy' size='340' side='right' caption='[[5txy]], [[Resolution\|resolution]] 1.21Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5txy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TXY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TXY FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7Q1:(5R)-5-phenyl-1,3-oxazolidine-2,4-dione'>7Q1</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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=5txy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5txy OCA], [http://pdbe.org/5txy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5txy RCSB], [http://www.ebi.ac.uk/pdbsum/5txy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5txy 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: Ren~~, B., Peat, T.S.~~, Poulsen, S~~.-A.	+	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~~ of ~~by Fragment Screening on human carbonic anhydrase~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Poulsen, S.-A]]	+	<div class="pdbe-citations 5txy" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Carbonate dehydratase]]
		+	[[Category: Peat, T S]]
		+	[[Category: Poulsen, S A]]
	[[Category: Ren, B]]		[[Category: Ren, B]]
-	[[Category: ~~Peat, T.S~~]]	+	[[Category: Crystal]]
		+	[[Category: Crystallization]]
		+	[[Category: Human carbonic anhydrase]]
		+	[[Category: Lyase]]
		+	[[Category: Zinc binding chemotype]]

OCA at 13:52, 9 March 2017

OCA — Thu, 09 Mar 2017 13:52:27 GMT

←Older revision		Revision as of 13:52, 9 March 2017
Line 7:		Line 7:
	Description: Identification of a New Zinc Binding Chemotype of by Fragment Screening on human carbonic anhydrase		Description: Identification of a New Zinc Binding Chemotype of by Fragment Screening on human carbonic anhydrase
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Peat, T.S]]
	[[Category: Poulsen, S.-A]]		[[Category: Poulsen, S.-A]]
	[[Category: Ren, B]]		[[Category: Ren, B]]
		+	[[Category: Peat, T.S]]

OCA at 16:07, 1 February 2017

OCA — Wed, 01 Feb 2017 16:07:30 GMT

←Older revision		Revision as of 16:07, 1 February 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Ren, B., Peat, T.S., Poulsen, S.-A.		Authors: Ren, B., Peat, T.S., Poulsen, S.-A.

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

OCA — Fri, 09 Dec 2016 18:02:31 GMT

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

←Older revision

Revision as of 18:02, 9 December 2016

OCA: New page: '''Unreleased structure''' The entry 5txy is ON HOLD Authors: Ren, B., Peat, T.S., Poulsen, S.-A. Description: Identification of a New Zinc Binding Chemotype of by Fragment Screening o...

OCA — Fri, 09 Dec 2016 18:02:30 GMT

New page: '''Unreleased structure''' The entry 5txy is ON HOLD Authors: Ren, B., Peat, T.S., Poulsen, S.-A. Description: Identification of a New Zinc Binding Chemotype of by Fragment Screening o...

New page

'''Unreleased structure'''

The entry 5txy is ON HOLD

Authors: Ren, B., Peat, T.S., Poulsen, S.-A.

Description: Identification of a New Zinc Binding Chemotype of by Fragment Screening on human carbonic anhydrase
[[Category: Unreleased Structures]]
[[Category: Peat, T.S]]
[[Category: Poulsen, S.-A]]
[[Category: Ren, B]]