3t83 - Revision history

OCA at 08:37, 20 March 2024

OCA — Wed, 20 Mar 2024 08:37:22 GMT

←Older revision		Revision as of 08:37, 20 March 2024
Line 3:		Line 3:
	<StructureSection load='3t83' size='340' side='right'caption='[[3t83]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='3t83' size='340' side='right'caption='[[3t83]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3t83]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T83 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T83 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3t83]] 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=3T83 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T83 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG5:2,3,4-TRI-O-PROPANOYL-6-O-SULFAMOYL-BETA-D-GLUCOPYRANOSE'>MG5</scene>, <scene name='pdbligand=SG5:2,3,4-TRI-O-PROPANOYL-6-O-SULFAMOYL-ALPHA-D-GLUCOPYRANOSE'>SG5</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]] 1.8Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3t82\|3t82]], [[3t84\|3t84]], [[3t85\|3t85]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG5:2,3,4-TRI-O-PROPANOYL-6-O-SULFAMOYL-BETA-D-GLUCOPYRANOSE'>MG5</scene>, <scene name='pdbligand=SG5:2,3,4-TRI-O-PROPANOYL-6-O-SULFAMOYL-ALPHA-D-GLUCOPYRANOSE'>SG5</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 ([https://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'>[https://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [https://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=3t83 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t83 OCA], [https://pdbe.org/3t83 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t83 RCSB], [https://www.ebi.ac.uk/pdbsum/3t83 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t83 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=3t83 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t83 OCA], [https://pdbe.org/3t83 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t83 RCSB], [https://www.ebi.ac.uk/pdbsum/3t83 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t83 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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>	+	[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 ==
-	[[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>	+	[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 ==~~	+
-	Carbonic anhydrases (CAs) are enzymes whose endogenous reaction is the reversible hydration of CO(2) to give HCO(3)(-) and a proton. CA are also known to exhibit weak and promiscuous esterase activity toward activated esters. Here, we report a series of findings obtained with a set of CA inhibitors that showed quite unexpectedly that the compounds were both inhibitors of CO(2) hydration and substrates for the esterase activity of CA. The compounds comprised a monosaccharide core with the C-6 primary hydroxyl group derivatized as a sulfamate (for CA recognition). The remaining four sugar hydroxyl groups were acylated. Using protein X-ray crystallography, the crystal structures of human CA II in complex with four of the sulfamate inhibitors were obtained. As expected, the four structures displayed the canonical CA protein-sulfamate interactions. Unexpectedly, a free hydroxyl group was observed at the anomeric center (C-1) rather than the parent C-1 acyl group. In addition, this hydroxyl group is observed axial to the carbohydrate ring while in the parent structure it is equatorial. A mechanism is proposed that accounts for this inversion of stereochemistry. For three of the inhibitors, the acyl groups at C-2 or at C-2 and C-3 were also absent with hydroxyl groups observed in their place and retention of stereochemistry. With the use of electrospray ionization-Fourier transform ion cyclotron resonance-mass spectrometry (ESI-FTICR-MS), we observed directly the sequential loss of all four acyl groups from one of the carbohydrate-based sulfamates. For this compound, the inhibitor and substrate binding mode were further analyzed using free energy calculations. These calculations suggested that the parent compound binds almost exclusively as a substrate. To conclude, we have demonstrated that acylated carbohydrate-based sulfamates are simultaneously inhibitor and substrate of human CA II. Our results suggest that, initially, the substrate binding mode dominates, but following hydrolysis, the ligand can also bind as a pure inhibitor thereby competing with the substrate binding mode.	+
-		+
-	Promiscuity of Carbonic Anhydrase II. Unexpected Ester Hydrolysis of Carbohydrate-Based Sulfamate Inhibitors.,Lopez M, Vu H, Wang CK, Wolf MG, Groenhof G, Innocenti A, Supuran CT, Poulsen SA J Am Chem Soc. 2011 Oct 19. PMID:21958118<ref>PMID:21958118</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3t83" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 30:		Line 19:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Carbonate dehydratase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Hofmann, A]]	+	[[Category: Hofmann A]]
-	[[Category: Wang~~, C K]]~~	+	[[Category: Wang CK]]
-	~~[[Category: Alpha carbonic anhydrase]]~~	+
-	~~[[Category: Lyase-lyase inhibitor complex~~]]	+

OCA at 16:47, 6 July 2022

OCA — Wed, 06 Jul 2022 16:47:03 GMT

←Older revision		Revision as of 16:47, 6 July 2022
Line 1:		Line 1:

	==Human Carbonic Anhydrase II in complex with Acetylated Carbohydrate Sulfamates==		==Human Carbonic Anhydrase II in complex with Acetylated Carbohydrate Sulfamates==
-	<StructureSection load='3t83' size='340' side='right' caption='[[3t83]], [[Resolution\|resolution]] 1.80Å' scene=''>	+	<StructureSection load='3t83' size='340' side='right'caption='[[3t83]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3t83]] 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=3T83 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3T83 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3t83]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T83 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T83 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG5:2,3,4-TRI-O-PROPANOYL-6-O-SULFAMOYL-BETA-D-GLUCOPYRANOSE'>MG5</scene>, <scene name='pdbligand=SG5:2,3,4-TRI-O-PROPANOYL-6-O-SULFAMOYL-ALPHA-D-GLUCOPYRANOSE'>SG5</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" id="ligandDat"><scene name='pdbligand=MG5:2,3,4-TRI-O-PROPANOYL-6-O-SULFAMOYL-BETA-D-GLUCOPYRANOSE'>MG5</scene>, <scene name='pdbligand=SG5:2,3,4-TRI-O-PROPANOYL-6-O-SULFAMOYL-ALPHA-D-GLUCOPYRANOSE'>SG5</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">[[3t82\|3t82]], [[3t84\|3t84]], [[3t85\|3t85]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3t82\|3t82]], [[3t84\|3t84]], [[3t85\|3t85]]</div></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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CA2 ([https://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'>[https://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [https://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=3t83 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t83 OCA], [~~http~~://pdbe.org/3t83 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3t83 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3t83 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3t83 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=3t83 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t83 OCA], [https://pdbe.org/3t83 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t83 RCSB], [https://www.ebi.ac.uk/pdbsum/3t83 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t83 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 25:		Line 25:

	==See Also==		==See Also==
-	*[[Carbonic anhydrase\|Carbonic anhydrase]]	+	*[[Carbonic anhydrase 3D structures\|Carbonic anhydrase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 32:		Line 32:
	[[Category: Carbonate dehydratase]]		[[Category: Carbonate dehydratase]]
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Hofmann, A]]		[[Category: Hofmann, A]]
	[[Category: Wang, C K]]		[[Category: Wang, C K]]
	[[Category: Alpha carbonic anhydrase]]		[[Category: Alpha carbonic anhydrase]]
	[[Category: Lyase-lyase inhibitor complex]]		[[Category: Lyase-lyase inhibitor complex]]

OCA at 18:51, 4 August 2016

OCA — Thu, 04 Aug 2016 18:51:31 GMT

←Older revision		Revision as of 18:51, 4 August 2016
Line 1:		Line 1:
		+
	==Human Carbonic Anhydrase II in complex with Acetylated Carbohydrate Sulfamates==		==Human Carbonic Anhydrase II in complex with Acetylated Carbohydrate Sulfamates==
	<StructureSection load='3t83' size='340' side='right' caption='[[3t83]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='3t83' size='340' side='right' caption='[[3t83]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3t83]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T83 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T83 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3t83]] 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=3T83 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T83 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG5:2,3,4-TRI-O-PROPANOYL-6-O-SULFAMOYL-BETA-D-GLUCOPYRANOSE'>MG5</scene>, <scene name='pdbligand=SG5:2,3,4-TRI-O-PROPANOYL-6-O-SULFAMOYL-ALPHA-D-GLUCOPYRANOSE'>SG5</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=MG5:2,3,4-TRI-O-PROPANOYL-6-O-SULFAMOYL-BETA-D-GLUCOPYRANOSE'>MG5</scene>, <scene name='pdbligand=SG5:2,3,4-TRI-O-PROPANOYL-6-O-SULFAMOYL-ALPHA-D-GLUCOPYRANOSE'>SG5</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">[[3t82\|3t82]], [[3t84\|3t84]], [[3t85\|3t85]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3t82\|3t82]], [[3t84\|3t84]], [[3t85\|3t85]]</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 ~~Homo sapiens~~])</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=3t83 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t83 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3t83 RCSB], [http://www.ebi.ac.uk/pdbsum/3t83 PDBsum]</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=3t83 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t83 OCA], [http://pdbe.org/3t83 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3t83 RCSB], [http://www.ebi.ac.uk/pdbsum/3t83 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3t83 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3t83" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 29:		Line 31:
	</StructureSection>		</StructureSection>
	[[Category: Carbonate dehydratase]]		[[Category: Carbonate dehydratase]]
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Hofmann, A]]		[[Category: Hofmann, A]]
	[[Category: Wang, C K]]		[[Category: Wang, C K]]
	[[Category: Alpha carbonic anhydrase]]		[[Category: Alpha carbonic anhydrase]]
	[[Category: Lyase-lyase inhibitor complex]]		[[Category: Lyase-lyase inhibitor complex]]

OCA at 07:29, 21 December 2014

OCA — Sun, 21 Dec 2014 07:29:22 GMT

←Older revision		Revision as of 07:29, 21 December 2014
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-	~~{{STRUCTURE_3t83\| PDB=3t83 \| SCENE= }}~~	+	==Human Carbonic Anhydrase II in complex with Acetylated Carbohydrate Sulfamates==
-	===Human Carbonic Anhydrase II in complex with Acetylated Carbohydrate Sulfamates===	+	<StructureSection load='3t83' size='340' side='right' caption='[[3t83]], [[Resolution\|resolution]] 1.80Å' scene=''>
-	~~{{ABSTRACT_PUBMED_21958118}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[3t83]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T83 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T83 FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG5:2,3,4-TRI-O-PROPANOYL-6-O-SULFAMOYL-BETA-D-GLUCOPYRANOSE'>MG5</scene>, <scene name='pdbligand=SG5:2,3,4-TRI-O-PROPANOYL-6-O-SULFAMOYL-ALPHA-D-GLUCOPYRANOSE'>SG5</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">[[3t82\|3t82]], [[3t84\|3t84]], [[3t85\|3t85]]</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 Homo sapiens])</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=3t83 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t83 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3t83 RCSB], [http://www.ebi.ac.uk/pdbsum/3t83 PDBsum]</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>		[[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 ==
-	==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>		[[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 enzymes whose endogenous reaction is the reversible hydration of CO(2) to give HCO(3)(-) and a proton. CA are also known to exhibit weak and promiscuous esterase activity toward activated esters. Here, we report a series of findings obtained with a set of CA inhibitors that showed quite unexpectedly that the compounds were both inhibitors of CO(2) hydration and substrates for the esterase activity of CA. The compounds comprised a monosaccharide core with the C-6 primary hydroxyl group derivatized as a sulfamate (for CA recognition). The remaining four sugar hydroxyl groups were acylated. Using protein X-ray crystallography, the crystal structures of human CA II in complex with four of the sulfamate inhibitors were obtained. As expected, the four structures displayed the canonical CA protein-sulfamate interactions. Unexpectedly, a free hydroxyl group was observed at the anomeric center (C-1) rather than the parent C-1 acyl group. In addition, this hydroxyl group is observed axial to the carbohydrate ring while in the parent structure it is equatorial. A mechanism is proposed that accounts for this inversion of stereochemistry. For three of the inhibitors, the acyl groups at C-2 or at C-2 and C-3 were also absent with hydroxyl groups observed in their place and retention of stereochemistry. With the use of electrospray ionization-Fourier transform ion cyclotron resonance-mass spectrometry (ESI-FTICR-MS), we observed directly the sequential loss of all four acyl groups from one of the carbohydrate-based sulfamates. For this compound, the inhibitor and substrate binding mode were further analyzed using free energy calculations. These calculations suggested that the parent compound binds almost exclusively as a substrate. To conclude, we have demonstrated that acylated carbohydrate-based sulfamates are simultaneously inhibitor and substrate of human CA II. Our results suggest that, initially, the substrate binding mode dominates, but following hydrolysis, the ligand can also bind as a pure inhibitor thereby competing with the substrate binding mode.

-	~~==About this Structure==~~	+	Promiscuity of Carbonic Anhydrase II. Unexpected Ester Hydrolysis of Carbohydrate-Based Sulfamate Inhibitors.,Lopez M, Vu H, Wang CK, Wolf MG, Groenhof G, Innocenti A, Supuran CT, Poulsen SA J Am Chem Soc. 2011 Oct 19. PMID:21958118<ref>PMID:21958118</ref>
-	~~[[3t83]] is a 1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http~~://~~oca~~.~~weizmann~~.ac.il/~~oca-bin/ocashort?id=3T83 OCA].~~	+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

	==See Also==		==See Also==
	*[[Carbonic anhydrase\|Carbonic anhydrase]]		*[[Carbonic anhydrase\|Carbonic anhydrase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:021958118</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Carbonate dehydratase]]		[[Category: Carbonate dehydratase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Hofmann, A.]]	+	[[Category: Hofmann, A]]
-	[[Category: Wang, C K.]]	+	[[Category: Wang, C K]]
	[[Category: Alpha carbonic anhydrase]]		[[Category: Alpha carbonic anhydrase]]
	[[Category: Lyase-lyase inhibitor complex]]		[[Category: Lyase-lyase inhibitor complex]]

OCA at 14:28, 10 July 2013

OCA — Wed, 10 Jul 2013 14:28:10 GMT

←Older revision		Revision as of 14:28, 10 July 2013
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	==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>	+	[[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==		==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>	+	[[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>

	==About this Structure==		==About this Structure==

OCA at 00:45, 25 March 2013

OCA — Mon, 25 Mar 2013 00:45:34 GMT

←Older revision		Revision as of 00:45, 25 March 2013
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-	[[Image:3t83.png\|left\|200px]]
-
	{{STRUCTURE_3t83\| PDB=3t83 \| SCENE= }}		{{STRUCTURE_3t83\| PDB=3t83 \| SCENE= }}
-
	===Human Carbonic Anhydrase II in complex with Acetylated Carbohydrate Sulfamates===		===Human Carbonic Anhydrase II in complex with Acetylated Carbohydrate Sulfamates===
		+	{{ABSTRACT_PUBMED_21958118}}

-	~~{{ABSTRACT_PUBMED_21958118}}~~	+	==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>

	==About this Structure==		==About this Structure==
Line 14:		Line 16:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:021958118</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021958118</ref><references group="xtra"/><references/>
	[[Category: Carbonate dehydratase]]		[[Category: Carbonate dehydratase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 07:55, 20 October 2012

OCA — Sat, 20 Oct 2012 07:55:48 GMT

←Older revision		Revision as of 07:55, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3t83]] is a 1 chain structure ~~of [[Carbonic anhydrase]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T83 OCA].	+	[[3t83]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T83 OCA].

	==See Also==		==See Also==

OCA at 17:54, 25 July 2012

OCA — Wed, 25 Jul 2012 17:54:57 GMT

←Older revision		Revision as of 17:54, 25 July 2012
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	[[Image:3t83.png\|left\|200px]]		[[Image:3t83.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3t83", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3t83\| PDB=3t83 \| SCENE= }}		{{STRUCTURE_3t83\| PDB=3t83 \| SCENE= }}

	===Human Carbonic Anhydrase II in complex with Acetylated Carbohydrate Sulfamates===		===Human Carbonic Anhydrase II in complex with Acetylated Carbohydrate Sulfamates===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_21958118}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 21958118 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_21958118}}		{{ABSTRACT_PUBMED_21958118}}

	==About this Structure==		==About this Structure==
-	[[3t83]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T83 OCA].	+	[[3t83]] is a 1 chain structure of [[Carbonic anhydrase]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T83 OCA].
		+
		+	==See Also==
		+	*[[Carbonic anhydrase\|Carbonic anhydrase]]

	==Reference==		==Reference==

OCA at 10:22, 30 October 2011

OCA — Sun, 30 Oct 2011 10:22:06 GMT

←Older revision		Revision as of 10:22, 30 October 2011
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-	~~'''Unreleased structure'''~~	+	[[Image:3t83.png\|left\|200px]]

-	The ~~entry 3t83~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3t83", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3t83\| PDB=3t83 \| SCENE= }}

-	~~Authors: Hofmann, A., Wang, C.K.~~	+	===Human Carbonic Anhydrase II in complex with Acetylated Carbohydrate Sulfamates===

-	~~Description~~: ~~Human Carbonic Anhydrase II in complex~~ with ~~Acetylated Carbohydrate Sulfamates~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21958118}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21958118 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21958118}}
		+
		+	==About this Structure==
		+	[[3t83]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T83 OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021958118</ref><references group="xtra"/>
		+	[[Category: Carbonate dehydratase]]
		+	[[Category: Homo sapiens]]
		+	[[Category: Hofmann, A.]]
		+	[[Category: Wang, C K.]]
		+	[[Category: Alpha carbonic anhydrase]]
		+	[[Category: Lyase-lyase inhibitor complex]]

OCA at 05:45, 7 September 2011

OCA — Wed, 07 Sep 2011 05:45:28 GMT

←Older revision		Revision as of 05:45, 7 September 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3t83 is ON HOLD	+	The entry 3t83 is ON HOLD until Paper Publication

	Authors: Hofmann, A., Wang, C.K.		Authors: Hofmann, A., Wang, C.K.

	Description: Human Carbonic Anhydrase II in complex with Acetylated Carbohydrate Sulfamates		Description: Human Carbonic Anhydrase II in complex with Acetylated Carbohydrate Sulfamates