6yh4 - Revision history

OCA at 13:26, 24 January 2024

OCA — Wed, 24 Jan 2024 13:26:55 GMT

←Older revision		Revision as of 13:26, 24 January 2024
Line 3:		Line 3:
	<StructureSection load='6yh4' size='340' side='right'caption='[[6yh4]], [[Resolution\|resolution]] 1.30Å' scene=''>		<StructureSection load='6yh4' size='340' side='right'caption='[[6yh4]], [[Resolution\|resolution]] 1.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6yh4]] 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=6YH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YH4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6yh4]] 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=6YH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YH4 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=V13:2,3,5,6-TETRAFLUORO-4-[(2-HYDROXYETHYL)SULFONYL]BENZENESULFONAMIDE'>V13</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]] 1.3Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=V13:2,3,5,6-TETRAFLUORO-4-[(2-HYDROXYETHYL)SULFONYL]BENZENESULFONAMIDE'>V13</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'>[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=6yh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yh4 OCA], [https://pdbe.org/6yh4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yh4 RCSB], [https://www.ebi.ac.uk/pdbsum/6yh4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yh4 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=6yh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yh4 OCA], [https://pdbe.org/6yh4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yh4 RCSB], [https://www.ebi.ac.uk/pdbsum/6yh4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yh4 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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Carbonate dehydratase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Grazulis, S]]	+	[[Category: Grazulis S]]
-	[[Category: Manakova, E]]	+	[[Category: Manakova E]]
-	[[Category: Smirnov, A]]	+	[[Category: Smirnov A]]
-	~~[[Category: Benzenesulfonamide]]~~	+
-	~~[[Category: Carbonic anhydrase]]~~	+
-	~~[[Category: Drug design]]~~	+
-	~~[[Category: Lyase]]~~	+
-	~~[[Category: Lyase-lyase inhibitor complex]]~~	+
-	~~[[Category: Metal-binding~~]]	+

OCA at 14:45, 2 June 2021

OCA — Wed, 02 Jun 2021 14:45:59 GMT

←Older revision		Revision as of 14:45, 2 June 2021
Line 1:		Line 1:

	==Crystal structure of chimeric carbonic anhydrase XII with 2,3,5,6-Tetrafluoro-4-(propylthio)benzenesulfonamide==		==Crystal structure of chimeric carbonic anhydrase XII with 2,3,5,6-Tetrafluoro-4-(propylthio)benzenesulfonamide==
-	<StructureSection load='6yh4' size='340' side='right'caption='[[6yh4]]' scene=''>	+	<StructureSection load='6yh4' size='340' side='right'caption='[[6yh4]], [[Resolution\|resolution]] 1.30Å' 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=6YH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YH4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6yh4]] 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=6YH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YH4 FirstGlance]. <br>
-	</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=6yh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yh4 OCA], [https://pdbe.org/6yh4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yh4 RCSB], [https://www.ebi.ac.uk/pdbsum/6yh4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yh4 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=V13:2,3,5,6-TETRAFLUORO-4-[(2-HYDROXYETHYL)SULFONYL]BENZENESULFONAMIDE'>V13</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=6yh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yh4 OCA], [https://pdbe.org/6yh4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yh4 RCSB], [https://www.ebi.ac.uk/pdbsum/6yh4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yh4 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 ==
		+	A key part of the optimization of small molecules in pharmaceutical inhibitor development is to vary the molecular design to enhance complementarity of chemical features of the compound with the positioning of amino acids in the active site of a target enzyme. Typically this involves iterations of synthesis, to modify the compound, and biophysical assay, to assess the outcomes. Selective targeting of the anti-cancer carbonic anhydrase isoform XII (CA XII), this process is challenging because the overall fold is very similar across the twelve CA isoforms. To enhance drug development for CA XII we used a reverse engineering approach where mutation of the key six amino acids in the active site of human CA XII into the CA II isoform was performed to provide a protein chimera (chCA XII) which is amenable to structure-based compound optimization. Through determination of structural detail and affinity measurement of the interaction with over 60 compounds we observed that the compounds that bound CA XII more strongly than CA II, switched their preference and bound more strongly to the engineered chimera, chCA XII, based on CA II, but containing the 6 key amino acids from CA XII, behaved as CA XII in its compound recognition profile. The structures of the compounds in the chimeric active site also resembled those determined for complexes with CA XII, hence validating this protein engineering approach in the development of new inhibitors.
		+
		+	Switching the Inhibitor-Enzyme Recognition Profile via Chimeric Carbonic Anhydrase XII.,Smirnoviene J, Smirnov A, Zaksauskas A, Zubriene A, Petrauskas V, Mickeviciute A, Michailoviene V, Capkauskaite E, Manakova E, Grazulis S, Baranauskiene L, Chen WY, Ladbury JE, Matulis D ChemistryOpen. 2021 May;10(5):567-580. doi: 10.1002/open.202100042. PMID:33945229<ref>PMID:33945229</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6yh4" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Carbonic anhydrase 3D structures\|Carbonic anhydrase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Carbonate dehydratase]]
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Grazulis S]]	+	[[Category: Grazulis, S]]
-	[[Category: Manakova E]]	+	[[Category: Manakova, E]]
-	[[Category: Smirnov A]]	+	[[Category: Smirnov, A]]
		+	[[Category: Benzenesulfonamide]]
		+	[[Category: Carbonic anhydrase]]
		+	[[Category: Drug design]]
		+	[[Category: Lyase]]
		+	[[Category: Lyase-lyase inhibitor complex]]
		+	[[Category: Metal-binding]]

OCA at 06:45, 7 April 2021

OCA — Wed, 07 Apr 2021 06:45:51 GMT

←Older revision		Revision as of 06:45, 7 April 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6yh4 is ON HOLD until Paper Publication~~	+	==Crystal structure of chimeric carbonic anhydrase XII with 2,3,5,6-Tetrafluoro-4-(propylthio)benzenesulfonamide==
-		+	<StructureSection load='6yh4' size='340' side='right'caption='[[6yh4]]' scene=''>
-	~~Authors: Smirnov, A., Manakova, E., Grazulis, S.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YH4 FirstGlance]. <br>
-	~~Description:~~ Crystal structure of chimeric carbonic anhydrase XII with 2,3,5,6-Tetrafluoro-4-(propylthio)benzenesulfonamide	+	</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=6yh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yh4 OCA], [https://pdbe.org/6yh4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yh4 RCSB], [https://www.ebi.ac.uk/pdbsum/6yh4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yh4 ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Manakova~~, E]]	+	__TOC__
-	[[Category: ~~Smirnov, A~~]]	+	</StructureSection>
-	[[Category: Grazulis, S]]	+	[[Category: Large Structures]]
		+	[[Category: Grazulis S]]
		+	[[Category: Manakova E]]
		+	[[Category: Smirnov A]]

OCA at 04:36, 6 May 2020

OCA — Wed, 06 May 2020 04:36:22 GMT

←Older revision		Revision as of 04:36, 6 May 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6yh4 is ON HOLD	+	The entry 6yh4 is ON HOLD until Paper Publication

	Authors: Smirnov, A., Manakova, E., Grazulis, S.		Authors: Smirnov, A., Manakova, E., Grazulis, S.
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	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Manakova, E]]		[[Category: Manakova, E]]
-	[[Category: Grazulis, S]]
	[[Category: Smirnov, A]]		[[Category: Smirnov, A]]
		+	[[Category: Grazulis, S]]

OCA: Protected "6yh4" [edit=sysop:move=sysop]

OCA — Wed, 08 Apr 2020 05:43:08 GMT

Protected "6yh4" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:43, 8 April 2020

OCA: New page: '''Unreleased structure''' The entry 6yh4 is ON HOLD Authors: Smirnov, A., Manakova, E., Grazulis, S. Description: Crystal structure of chimeric carbonic anhydrase XII with 2,3,5,6-Tet...

OCA — Wed, 08 Apr 2020 05:43:07 GMT

New page: '''Unreleased structure''' The entry 6yh4 is ON HOLD Authors: Smirnov, A., Manakova, E., Grazulis, S. Description: Crystal structure of chimeric carbonic anhydrase XII with 2,3,5,6-Tet...

New page

'''Unreleased structure'''

The entry 6yh4 is ON HOLD

Authors: Smirnov, A., Manakova, E., Grazulis, S.

Description: Crystal structure of chimeric carbonic anhydrase XII with 2,3,5,6-Tetrafluoro-4-(propylthio)benzenesulfonamide
[[Category: Unreleased Structures]]
[[Category: Manakova, E]]
[[Category: Grazulis, S]]
[[Category: Smirnov, A]]