5sz4 - Revision history

OCA at 12:51, 4 October 2023

OCA — Wed, 04 Oct 2023 12:51:51 GMT

←Older revision		Revision as of 12:51, 4 October 2023
Line 1:		Line 1:

	==Carbonic anhydrase IX-mimic in complex with 4-(phenyl)-benzenesulfonamide==		==Carbonic anhydrase IX-mimic in complex with 4-(phenyl)-benzenesulfonamide==
-	<StructureSection load='5sz4' size='340' side='right' caption='[[5sz4]], [[Resolution\|resolution]] 1.60Å' scene=''>	+	<StructureSection load='5sz4' size='340' side='right'caption='[[5sz4]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5sz4]] 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=5SZ4 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5SZ4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5sz4]] 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=5SZ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SZ4 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=72D:4-(PHENYL)-BENZENESULFONAMIDE'>72D</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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]] 1.6Å</td></tr>
-	~~<tr~~ id~~='related'><td class~~="~~sblockLbl~~">~~<b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5sz0\|5sz0]]~~, [[~~5sz1~~\|~~5sz1]], [[5sz2\|5sz2]], [[5sz3\|5sz3]], [[5sz5\|5sz5]], [[5sz6\|5sz6]], [[5sz7\|5sz7~~]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=72D:4-(PHENYL)-BENZENESULFONAMIDE'>72D</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5sz4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sz4 OCA], [https://pdbe.org/5sz4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5sz4 RCSB], [https://www.ebi.ac.uk/pdbsum/5sz4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5sz4 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/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=5sz4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sz4 OCA], [~~http~~://pdbe.org/5sz4 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5sz4 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5sz4 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5sz4 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 23:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5sz4" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5sz4" 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: ~~Human~~]]	+	[[Category: Large Structures]]
-	[[Category: Bhatt, A]]	+	[[Category: Bhatt A]]
-	[[Category: Cornelio, B]]	+	[[Category: Cornelio B]]
-	[[Category: Mahon~~, B P~~]]	+	[[Category: Mahon BP]]
-	[[Category: McKenna, R]]	+	[[Category: McKenna R]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Lyase-lyase inhibitor complex]]~~	+
-	~~[[Category: Sulfonamide]]~~	+
-	~~[[Category: Zinc-binding~~]]	+

OCA at 14:19, 6 November 2017

OCA — Mon, 06 Nov 2017 14:19:37 GMT

←Older revision		Revision as of 14:19, 6 November 2017
Line 3:		Line 3:
	<StructureSection load='5sz4' size='340' side='right' caption='[[5sz4]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='5sz4' size='340' side='right' caption='[[5sz4]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5sz4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SZ4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5SZ4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5sz4]] 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=5SZ4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5SZ4 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=72D:4-(PHENYL)-BENZENESULFONAMIDE'>72D</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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=72D:4-(PHENYL)-BENZENESULFONAMIDE'>72D</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5sz0\|5sz0]], [[5sz1\|5sz1]], [[5sz2\|5sz2]], [[5sz3\|5sz3]], [[5sz5\|5sz5]], [[5sz6\|5sz6]], [[5sz7\|5sz7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5sz0\|5sz0]], [[5sz1\|5sz1]], [[5sz2\|5sz2]], [[5sz3\|5sz3]], [[5sz5\|5sz5]], [[5sz6\|5sz6]], [[5sz7\|5sz7]]</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=5sz4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sz4 OCA], [http://pdbe.org/5sz4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5sz4 RCSB], [http://www.ebi.ac.uk/pdbsum/5sz4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5sz4 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=5sz4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sz4 OCA], [http://pdbe.org/5sz4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5sz4 RCSB], [http://www.ebi.ac.uk/pdbsum/5sz4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5sz4 ProSAT]</span></td></tr>
Line 27:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Carbonate dehydratase]]		[[Category: Carbonate dehydratase]]
		+	[[Category: Human]]
	[[Category: Bhatt, A]]		[[Category: Bhatt, A]]
	[[Category: Cornelio, B]]		[[Category: Cornelio, B]]

OCA at 21:30, 22 December 2016

OCA — Thu, 22 Dec 2016 21:30:43 GMT

←Older revision		Revision as of 21:30, 22 December 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5sz4 is ~~ON HOLD~~	+	==Carbonic anhydrase IX-mimic in complex with 4-(phenyl)-benzenesulfonamide==
		+	<StructureSection load='5sz4' size='340' side='right' caption='[[5sz4]], [[Resolution\|resolution]] 1.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5sz4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SZ4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5SZ4 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=72D:4-(PHENYL)-BENZENESULFONAMIDE'>72D</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5sz0\|5sz0]], [[5sz1\|5sz1]], [[5sz2\|5sz2]], [[5sz3\|5sz3]], [[5sz5\|5sz5]], [[5sz6\|5sz6]], [[5sz7\|5sz7]]</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=5sz4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sz4 OCA], [http://pdbe.org/5sz4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5sz4 RCSB], [http://www.ebi.ac.uk/pdbsum/5sz4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5sz4 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 ==
		+	Carbonic anhydrases (CAs) are implicated in a wide range of diseases, including the upregulation of isoforms CA IX and XII in many aggressive cancers. However, effective inhibition of disease-implicated CAs should minimally affect the ubiquitously expressed isoforms including CA I and II to improve directed distribution of the inhibitors to the cancer-associated isoforms and reduce side effects. Four benzenesulfonamide-based inhibitors were synthesized using the "tail approach" and display nM affinities for several CA isoforms. The crystal structures of the inhibitors bound to a CA IX-mimic and CA II are presented. Further in-silico modeling was performed with the inhibitors docked into CA I and XII to identify residues that contribute to or hinder their binding interactions. These structural studies demonstrate that active site residues lining the hydrophobic pocket, especially positions 92 and 131, dictate the positional binding and affinity of inhibitors and the tail groups modulate CA isoform specificity. Geometry optimizations were performed on each ligand in the crystal structures and showed the energetic penalties of the inhibitors' conformations were negligible compared to the gain of active site interactions. These studies further our understanding of obtaining isoform specificity when designing small molecule CA inhibitors.

-	~~Authors: Bhatt~~, A., Mahon, ~~B.P.~~, Cornelio, B., ~~McKenna~~, R.	+	Structure activity relationships of benzenesulfonamide-based inhibitors towards carbonic anhydrase isoform specificity.,Bhatt A, Mahon BP, Cruzeiro VW, Cornelio B, Laronze-Cochard M, Ceruso M, Sapi J, Rance GA, Khlobystov AN, Fontana A, Roitberg A, Supuran CT, Mc Kenna R Chembiochem. 2016 Nov 18. doi: 10.1002/cbic.201600513. PMID:27860128<ref>PMID:27860128</ref>

-	~~Description: Carbonic anhydrase IX~~-~~mimic in complex with 4~~-~~(phenyl)-benzenesulfonamide~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5sz4" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Carbonate dehydratase]]
	[[Category: Bhatt, A]]		[[Category: Bhatt, A]]
	[[Category: Cornelio, B]]		[[Category: Cornelio, B]]
-	[[Category: ~~Mckenna~~, R]]	+	[[Category: Mahon, B P]]
-	[[Category: ~~Mahon~~, ~~B.P~~]]	+	[[Category: McKenna, R]]
		+	[[Category: Inhibitor]]
		+	[[Category: Lyase-lyase inhibitor complex]]
		+	[[Category: Sulfonamide]]
		+	[[Category: Zinc-binding]]

OCA at 12:03, 21 September 2016

OCA — Wed, 21 Sep 2016 12:03:18 GMT

←Older revision		Revision as of 12:03, 21 September 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5sz4 is ON HOLD ~~until sometime in the future~~	+	The entry 5sz4 is ON HOLD

	Authors: Bhatt, A., Mahon, B.P., Cornelio, B., McKenna, R.		Authors: Bhatt, A., Mahon, B.P., Cornelio, B., McKenna, R.

OCA: Protected "5sz4" [edit=sysop:move=sysop]

OCA — Fri, 09 Sep 2016 15:26:43 GMT

Protected "5sz4" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:26, 9 September 2016

OCA: New page: '''Unreleased structure''' The entry 5sz4 is ON HOLD until sometime in the future Authors: Bhatt, A., Mahon, B.P., Cornelio, B., McKenna, R. Description: Carbonic anhydrase IX-mimic in...

OCA — Fri, 09 Sep 2016 15:26:42 GMT

New page: '''Unreleased structure''' The entry 5sz4 is ON HOLD until sometime in the future Authors: Bhatt, A., Mahon, B.P., Cornelio, B., McKenna, R. Description: Carbonic anhydrase IX-mimic in...

New page

'''Unreleased structure'''

The entry 5sz4 is ON HOLD until sometime in the future

Authors: Bhatt, A., Mahon, B.P., Cornelio, B., McKenna, R.

Description: Carbonic anhydrase IX-mimic in complex with 4-(phenyl)-benzenesulfonamide
[[Category: Unreleased Structures]]
[[Category: Bhatt, A]]
[[Category: Cornelio, B]]
[[Category: Mckenna, R]]
[[Category: Mahon, B.P]]