OCA at 12:26, 24 January 2024

OCA — Wed, 24 Jan 2024 12:26:59 GMT

←Older revision		Revision as of 12:26, 24 January 2024
Line 1:		Line 1:

	==Human Carbonic Anhydrase II in complex with fluorinated benzenesulfonamide==		==Human Carbonic Anhydrase II in complex with fluorinated benzenesulfonamide==
-	<StructureSection load='6rri' size='340' side='right'caption='[[6rri]]' scene=''>	+	<StructureSection load='6rri' size='340' side='right'caption='[[6rri]], [[Resolution\|resolution]] 1.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RRI OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6RRI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6rri]] 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=6RRI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RRI FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6rri FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rri OCA], [~~http~~://pdbe.org/6rri PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6rri RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6rri PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6rri ProSAT]</span></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]] 1.097Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BE7:(4-CARBOXYPHENYL)(CHLORO)MERCURY'>BE7</scene>, <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=KFH:2,3,5,6-tetrakis(fluoranyl)benzenesulfonamide'>KFH</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'>[https://proteopedia.org/fgij/fg.htm?mol=6rri FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rri OCA], [https://pdbe.org/6rri PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rri RCSB], [https://www.ebi.ac.uk/pdbsum/6rri PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rri ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[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 ==
		+	[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 fluorination of lead-like compounds is a common tool in medicinal chemistry to alter molecular properties in various ways and with different goals. We herein present a detailed study of the binding of fluorinated benzenesulfonamides to human Carbonic Anhydrase II by complementing macromolecular X-ray crystallographic observations with thermodynamic and kinetic data collected with the novel method of kinITC. Our findings comprise so far unknown alternative binding modes in the crystalline state for some of the investigated compounds as well as complex thermodynamic and kinetic structure-activity relationships. They suggest that fluorination of the benzenesulfonamide core is especially advantageous in one position with respect to the kinetic signatures of binding and that a higher degree of fluorination does not necessarily provide for a higher affinity or more favorable kinetic binding profiles. Lastly, we propose a relationship between the kinetics of binding and ligand acidity based on a small set of compounds with similar substitution patterns.
		+
		+	The Influence of Varying Fluorination Patterns on the Thermodynamics and Kinetics of Benzenesulfonamide Binding to Human Carbonic Anhydrase II.,Glockner S, Ngo K, Wagner B, Heine A, Klebe G Biomolecules. 2020 Mar 27;10(4). pii: biom10040509. doi: 10.3390/biom10040509. PMID:32230853<ref>PMID:32230853</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6rri" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Carbonic anhydrase 3D structures\|Carbonic anhydrase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Gloeckner S]]		[[Category: Gloeckner S]]
	[[Category: Heine A]]		[[Category: Heine A]]
	[[Category: Klebe G]]		[[Category: Klebe G]]

OCA at 06:57, 15 April 2020

OCA — Wed, 15 Apr 2020 06:57:35 GMT

←Older revision		Revision as of 06:57, 15 April 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6rri ~~is ON HOLD until Paper Publication~~	+	==Human Carbonic Anhydrase II in complex with fluorinated benzenesulfonamide==
-		+	<StructureSection load='6rri' size='340' side='right'caption='[[6rri]]' scene=''>
-	~~Authors~~: ~~Gloeckner~~, S., ~~Heine~~, A., ~~Klebe~~, G.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RRI OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6RRI FirstGlance]. <br>
-	~~Description: Human Carbonic Anhydrase II in complex with fluorinated benzenesulfonamide~~	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6rri FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rri OCA], [http://pdbe.org/6rri PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rri RCSB], [http://www.ebi.ac.uk/pdbsum/6rri PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rri ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Heine, A~~]]	+	__TOC__
-	[[Category: ~~Gloeckner, S~~]]	+	</StructureSection>
-	[[Category: Klebe, G]]	+	[[Category: Large Structures]]
		+	[[Category: Gloeckner S]]
		+	[[Category: Heine A]]
		+	[[Category: Klebe G]]

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

OCA — Wed, 29 May 2019 04:43:39 GMT

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

←Older revision

Revision as of 04:43, 29 May 2019

OCA: New page: '''Unreleased structure''' The entry 6rri is ON HOLD until Paper Publication Authors: Gloeckner, S., Heine, A., Klebe, G. Description: Human Carbonic Anhydrase II in complex with fluor...

OCA — Wed, 29 May 2019 04:43:37 GMT

New page: '''Unreleased structure''' The entry 6rri is ON HOLD until Paper Publication Authors: Gloeckner, S., Heine, A., Klebe, G. Description: Human Carbonic Anhydrase II in complex with fluor...

New page

'''Unreleased structure'''

The entry 6rri is ON HOLD until Paper Publication

Authors: Gloeckner, S., Heine, A., Klebe, G.

Description: Human Carbonic Anhydrase II in complex with fluorinated benzenesulfonamide
[[Category: Unreleased Structures]]
[[Category: Heine, A]]
[[Category: Gloeckner, S]]
[[Category: Klebe, G]]

6rri - Revision history

OCA at 12:26, 24 January 2024

OCA at 06:57, 15 April 2020

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

OCA: New page: '''Unreleased structure''' The entry 6rri is ON HOLD until Paper Publication Authors: Gloeckner, S., Heine, A., Klebe, G. Description: Human Carbonic Anhydrase II in complex with fluor...