6e8p - Revision history

OCA at 06:21, 11 October 2023

2023-10-11T06:21:04Z

←Older revision		Revision as of 06:21, 11 October 2023
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	<StructureSection load='6e8p' size='340' side='right'caption='[[6e8p]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='6e8p' size='340' side='right'caption='[[6e8p]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6e8p]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E8P OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6E8P FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6e8p]] 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=6E8P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E8P FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HZJ:(14beta,17beta)-estra-1(10),2,4,6,8-pentaene-3,17-diyl+disulfamate'>HZJ</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]] 1.9Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HZJ:(14beta,17beta)-estra-1(10),2,4,6,8-pentaene-3,17-diyl+disulfamate'>HZJ</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6e8p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e8p OCA], [~~http~~://pdbe.org/6e8p PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6e8p RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6e8p PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6e8p ProSAT]</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=6e8p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e8p OCA], [https://pdbe.org/6e8p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e8p RCSB], [https://www.ebi.ac.uk/pdbsum/6e8p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e8p 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 ==
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	</div>		</div>
	<div class="pdbe-citations 6e8p" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6e8p" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Carbonic anhydrase 3D structures\|Carbonic anhydrase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Carbonate dehydratase~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Andring~~, J T~~]]	+	[[Category: Andring JT]]
-	[[Category: Mckenna, R]]	+	[[Category: Mckenna R]]
-	~~[[Category: Carbonic anhydrase steroid sulfamate cancer]]~~	+
-	~~[[Category: Lyase~~]]	+

OCA at 06:54, 3 April 2019

2019-04-03T06:54:09Z

←Older revision		Revision as of 06:54, 3 April 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6e8p is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==CA IX mimic Complexed with Steroidal Sulfamate Compound STX 49==
		+	<StructureSection load='6e8p' size='340' side='right'caption='[[6e8p]], [[Resolution\|resolution]] 1.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6e8p]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E8P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E8P FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HZJ:(14beta,17beta)-estra-1(10),2,4,6,8-pentaene-3,17-diyl+disulfamate'>HZJ</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=6e8p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e8p OCA], [http://pdbe.org/6e8p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e8p RCSB], [http://www.ebi.ac.uk/pdbsum/6e8p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e8p 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 ==
		+	3,17beta-Bis-sulfamoyloxy-2-methoxyestra-1,3,5(10)-triene (STX140), a bis-sulfamate derivative of the endogenous steroid 2-methoxyestradiol, has shown promising anticancer potency both in vitro and in vivo, with excellent bioavailability. Its activity against taxane-resistant xenografts makes it a potential drug candidate against triple-negative breast cancer (TNBC). These properties are linked to the ability of STX140 to act in a multitargeting fashion in vivo as a microtubule disruptor, leading to cell cycle arrest and with both proapoptotic and anti-angiogenic activities. Carbonic anhydrase IX (CA IX) is a well-established biomarker for aggressive cancers, including TNBC. This study reports, for the first time, the inhibitory activities of a series of steroidal and nonsteroidal sulfamate derivatives against CA IX in comparison to the ubiquitous CA II, with some compounds demonstrating 100-200-fold selectivity for CA IX over CA II. X-ray crystallographic studies of four of the most promising compounds reveal that isoform-specific residue interactions are responsible for the high specificity.

-	~~Authors~~: Andring, J.T., ~~Mckenna, R~~.	+	3,17beta-Bis-sulfamoyloxy-2-methoxyestra-1,3,5(10)-triene and Nonsteroidal Sulfamate Derivatives Inhibit Carbonic Anhydrase IX: Structure-Activity Optimization for Isoform Selectivity.,Andring JT, Dohle W, Tu C, Potter BVL, McKenna R J Med Chem. 2019 Feb 28;62(4):2202-2212. doi: 10.1021/acs.jmedchem.8b01990. Epub , 2019 Feb 18. PMID:30721041<ref>PMID:30721041</ref>

-	~~Description~~: ~~CA IX mimic Complexed with Steroidal Sulfamate Compound STX 49~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Andring, J.T]]	+	<div class="pdbe-citations 6e8p" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Carbonate dehydratase]]
		+	[[Category: Large Structures]]
		+	[[Category: Andring, J T]]
	[[Category: Mckenna, R]]		[[Category: Mckenna, R]]
		+	[[Category: Carbonic anhydrase steroid sulfamate cancer]]
		+	[[Category: Lyase]]

OCA at 05:38, 29 August 2018

2018-08-29T05:38:25Z

←Older revision		Revision as of 05:38, 29 August 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6e8p is ON HOLD	+	The entry 6e8p is ON HOLD until Paper Publication

	Authors: Andring, J.T., Mckenna, R.		Authors: Andring, J.T., Mckenna, R.

OCA: Protected "6e8p" [edit=sysop:move=sysop]

2018-08-09T19:54:37Z

Protected "6e8p" [edit=sysop:move=sysop]

←Older revision

Revision as of 19:54, 9 August 2018

OCA: New page: '''Unreleased structure''' The entry 6e8p is ON HOLD Authors: Andring, J.T., Mckenna, R. Description: CA IX mimic Complexed with Steroidal Sulfamate Compound STX 49 [[Category: Unrelea...

2018-08-09T19:54:36Z

New page: '''Unreleased structure''' The entry 6e8p is ON HOLD Authors: Andring, J.T., Mckenna, R. Description: CA IX mimic Complexed with Steroidal Sulfamate Compound STX 49 [[Category: Unrelea...

New page

'''Unreleased structure'''

The entry 6e8p is ON HOLD

Authors: Andring, J.T., Mckenna, R.

Description: CA IX mimic Complexed with Steroidal Sulfamate Compound STX 49
[[Category: Unreleased Structures]]
[[Category: Andring, J.T]]
[[Category: Mckenna, R]]