7ca2 - Revision history

OCA at 14:51, 6 March 2024

2024-03-06T14:51:49Z

← Older revision		Revision as of 14:51, 6 March 2024
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	==ENGINEERING THE HYDROPHOBIC POCKET OF CARBONIC ANHYDRASE II==		==ENGINEERING THE HYDROPHOBIC POCKET OF CARBONIC ANHYDRASE II==
	<StructureSection load='7ca2' size='340' side='right' caption='[[7ca2]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='7ca2' size='340' side='right'caption='[[7ca2]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7ca2]] 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=7CA2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=7CA2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[7ca2]] 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=7CA2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CA2 FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name~~=~~'pdbligand=HG:MERCURY+(II)+ION'>HG</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]] 2.4Å</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=HG:MERCURY+(II)+ION'>HG</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=7ca2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ca2 OCA], [~~http~~://pdbe.org/7ca2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7ca2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7ca2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7ca2 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=7ca2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ca2 OCA], [https://pdbe.org/7ca2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ca2 RCSB], [https://www.ebi.ac.uk/pdbsum/7ca2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ca2 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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ca/7ca2_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ca/7ca2_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 22:		Line 22:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=7ca2 ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=7ca2 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Wild-type and mutant human carbonic anhydrases II, where mutations have been made in the hydrophobic pocket of the active site, have been studied by X-ray crystallographic methods. Specifically, mutations at Val-143 (the base of the pocket) lead to significant changes in catalytic activity and protein structure. The obliteration of a well-defined pocket in the Val-143----Phe and Val-143----Tyr mutants results in significantly diminished enzyme activity [(5 x 10(4))-fold and (3 x 10(5))-fold, respectively]; however, the activity of the Val-143----His mutant is diminished less (10(2)-fold), and deepening the pocket in the Val-143----Gly mutant results in only a 2-fold decrease in activity [Fierke et al., 1991 (preceding paper in this issue)]. These results indicate that the hydrophobic pocket is important for substrate association with the enzyme, but there are probably several catalytically acceptable substrate trajectories through this region of the enzyme structure. Additionally, each mutant protein exhibits long-range (ca. 10-15 A) compensatory structural changes which accommodate the Val-143 substitution. As such, the genetic-structural approach represented in this work serves as a three-dimensional paradigm for the redesign of specificity pockets in other protein catalysts.

	~~Engineering the hydrophobic pocket of carbonic anhydrase II.,Alexander RS, Nair SK, Christianson DW Biochemistry. 1991 Nov 19;30(46):11064-72. PMID:1932029<ref>PMID:1932029</ref>~~		==See Also==
			*[[Carbonic anhydrase 3D structures\|Carbonic anhydrase 3D structures]]
	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class~~=~~"pdbe-citations 7ca2" style~~=~~"background-color:#fffaf0;"></div>~~
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Carbonate dehydratase~~]]		[[Category: Homo sapiens]]
	[[Category: ~~Human~~]]		[[Category: Large Structures]]
	[[Category: Christianson~~, D W~~]]		[[Category: Christianson DW]]
	[[Category: Nair~~, S K~~]]		[[Category: Nair SK]]

OCA at 07:46, 29 November 2017

2017-11-29T07:46:04Z

← Older revision		Revision as of 07:46, 29 November 2017
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	</div>		</div>
	<div class="pdbe-citations 7ca2" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7ca2" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[Carbonic anhydrase\|Carbonic anhydrase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 19:30, 5 August 2016

2016-08-05T19:30:17Z

← Older revision		Revision as of 19:30, 5 August 2016
Line 1:		Line 1:

	==ENGINEERING THE HYDROPHOBIC POCKET OF CARBONIC ANHYDRASE II==		==ENGINEERING THE HYDROPHOBIC POCKET OF CARBONIC ANHYDRASE II==
	<StructureSection load='7ca2' size='340' side='right' caption='[[7ca2]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='7ca2' size='340' side='right' caption='[[7ca2]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7ca2]] 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=7CA2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=7CA2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[7ca2]] 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=7CA2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=7CA2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</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=HG:MERCURY+(II)+ION'>HG</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='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=7ca2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ca2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=7ca2 RCSB], [http://www.ebi.ac.uk/pdbsum/7ca2 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=7ca2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ca2 OCA], [http://pdbe.org/7ca2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7ca2 RCSB], [http://www.ebi.ac.uk/pdbsum/7ca2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7ca2 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=7ca2 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 29:		Line 30:
	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 7ca2" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 37:		Line 39:
	</StructureSection>		</StructureSection>
	[[Category: Carbonate dehydratase]]		[[Category: Carbonate dehydratase]]
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Christianson, D W]]		[[Category: Christianson, D W]]
	[[Category: Nair, S K]]		[[Category: Nair, S K]]

OCA at 15:05, 21 December 2014

2014-12-21T15:05:32Z

← Older revision		Revision as of 15:05, 21 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_7ca2~~\| ~~PDB~~=7ca2 \| ~~SCENE~~= }}		==ENGINEERING THE HYDROPHOBIC POCKET OF CARBONIC ANHYDRASE II==
	===~~ENGINEERING THE HYDROPHOBIC POCKET OF CARBONIC ANHYDRASE II~~===		<StructureSection load='7ca2' size='340' side='right' caption='[[7ca2]], [[Resolution\|resolution]] 2.40Å' scene=''>
	~~{{ABSTRACT_PUBMED_1932029}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[7ca2]] 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=7CA2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=7CA2 FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</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=7ca2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ca2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=7ca2 RCSB], [http://www.ebi.ac.uk/pdbsum/7ca2 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>
			== 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>
			== Evolutionary Conservation ==
			[[Image:Consurf_key_small.gif\|200px\|right]]
			Check<jmol>
			<jmolCheckbox>
			<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ca/7ca2_consurf.spt"</scriptWhenChecked>
			<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
			<text>to colour the structure by Evolutionary Conservation</text>
			</jmolCheckbox>
			</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
			<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Wild-type and mutant human carbonic anhydrases II, where mutations have been made in the hydrophobic pocket of the active site, have been studied by X-ray crystallographic methods. Specifically, mutations at Val-143 (the base of the pocket) lead to significant changes in catalytic activity and protein structure. The obliteration of a well-defined pocket in the Val-143----Phe and Val-143----Tyr mutants results in significantly diminished enzyme activity [(5 x 10(4))-fold and (3 x 10(5))-fold, respectively]; however, the activity of the Val-143----His mutant is diminished less (10(2)-fold), and deepening the pocket in the Val-143----Gly mutant results in only a 2-fold decrease in activity [Fierke et al., 1991 (preceding paper in this issue)]. These results indicate that the hydrophobic pocket is important for substrate association with the enzyme, but there are probably several catalytically acceptable substrate trajectories through this region of the enzyme structure. Additionally, each mutant protein exhibits long-range (ca. 10-15 A) compensatory structural changes which accommodate the Val-143 substitution. As such, the genetic-structural approach represented in this work serves as a three-dimensional paradigm for the redesign of specificity pockets in other protein catalysts.

	~~==Disease==~~		Engineering the hydrophobic pocket of carbonic anhydrase II.,Alexander RS, Nair SK, Christianson DW Biochemistry. 1991 Nov 19;30(46):11064-72. PMID:1932029<ref>PMID:1932029</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==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[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>

	~~==About this Structure==~~
	[[7ca2]] 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=7CA2 OCA].

	==See Also==		==See Also==
	*[[Carbonic anhydrase\|Carbonic anhydrase]]		*[[Carbonic anhydrase\|Carbonic anhydrase]]
			== References ==
	==~~Reference~~==		<references/>
	~~<ref group="xtra">PMID:001932029</ref>~~<references ~~group="xtra"~~/><~~references~~/>		__TOC__
			</StructureSection>
	[[Category: Carbonate dehydratase]]		[[Category: Carbonate dehydratase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Christianson, D W.]]		[[Category: Christianson, D W]]
	[[Category: Nair, S K.]]		[[Category: Nair, S K]]

OCA at 04:10, 25 March 2013

2013-03-25T04:10:35Z

← Older revision		Revision as of 04:10, 25 March 2013
Line 1:		Line 1:
	~~[[Image:7ca2.png\|left\|200px]]~~

	{{STRUCTURE_7ca2\| PDB=7ca2 \| SCENE= }}		{{STRUCTURE_7ca2\| PDB=7ca2 \| SCENE= }}
			===ENGINEERING THE HYDROPHOBIC POCKET OF CARBONIC ANHYDRASE II===
			{{ABSTRACT_PUBMED_1932029}}

	===~~ENGINEERING THE HYDROPHOBIC POCKET OF CARBONIC ANHYDRASE~~ II~~===~~		==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>

	~~{{ABSTRACT_PUBMED_1932029}}~~		==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==
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	==Reference==		==Reference==
	<ref group="xtra">PMID:001932029</ref><references group="xtra"/>		<ref group="xtra">PMID:001932029</ref><references group="xtra"/><references/>
	[[Category: Carbonate dehydratase]]		[[Category: Carbonate dehydratase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Christianson, D W.]]		[[Category: Christianson, D W.]]
	[[Category: Nair, S K.]]		[[Category: Nair, S K.]]

OCA at 21:47, 20 October 2012

2012-10-20T21:47:27Z

← Older revision		Revision as of 21:47, 20 October 2012
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	==About this Structure==		==About this Structure==
	[[7ca2]] 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=7CA2 OCA].		[[7ca2]] 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=7CA2 OCA].

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

OCA: Protected "7ca2" [edit=sysop:move=sysop]

2012-07-27T14:18:12Z

Protected "7ca2" [edit=sysop:move=sysop]

← Older revision	Revision as of 14:18, 27 July 2012
(No difference)

OCA at 14:18, 27 July 2012

2012-07-27T14:18:10Z

← Older revision		Revision as of 14:18, 27 July 2012
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	~~{{Seed}}~~
	[[Image:7ca2.png\|left\|200px]]		[[Image:7ca2.png\|left\|200px]]

	~~<!--~~
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	~~or leave the SCENE parameter empty for the default display.~~
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	{{STRUCTURE_7ca2\| PDB=7ca2 \| SCENE= }}		{{STRUCTURE_7ca2\| PDB=7ca2 \| SCENE= }}

	===ENGINEERING THE HYDROPHOBIC POCKET OF CARBONIC ANHYDRASE II===		===ENGINEERING THE HYDROPHOBIC POCKET OF CARBONIC ANHYDRASE II===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_1932029}}, adds the Publication Abstract to the page~~
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	~~-->~~
	{{ABSTRACT_PUBMED_1932029}}		{{ABSTRACT_PUBMED_1932029}}

	==About this Structure==		==About this Structure==
	~~7CA2~~ is a 1 chain structure of 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=7CA2 OCA].		[[7ca2]] 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=7CA2 OCA].

			==See Also==
			*[[Carbonic anhydrase\|Carbonic anhydrase]]

	==Reference==		==Reference==
	<ref group="xtra">PMID:~~1932029~~</ref><references group="xtra"/>		<ref group="xtra">PMID:001932029</ref><references group="xtra"/>
	[[Category: Carbonate dehydratase]]		[[Category: Carbonate dehydratase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Christianson, D W.]]		[[Category: Christianson, D W.]]
	[[Category: Nair, S K.]]		[[Category: Nair, S K.]]

	~~''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 07:56:16 2009''~~

OCA at 05:56, 18 February 2009

2009-02-18T05:56:17Z

← Older revision		Revision as of 05:56, 18 February 2009
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	==About this Structure==		==About this Structure==
	7CA2 is a ~~[[Single protein]]~~ structure of 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=7CA2 OCA].		7CA2 is a 1 chain structure of 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=7CA2 OCA].

	==Reference==		==Reference==
	~~Engineering the hydrophobic pocket of carbonic anhydrase II., Alexander RS, Nair SK, Christianson DW, Biochemistry. 1991 Nov 19;30(46):11064-72.~~ PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/1932029 1932029]~~		<ref group="xtra">PMID:1932029</ref><references group="xtra"/>
	[[Category: Carbonate dehydratase]]		[[Category: Carbonate dehydratase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	~~[[Category: Single protein]]~~
	[[Category: Christianson, D W.]]		[[Category: Christianson, D W.]]
	[[Category: Nair, S K.]]		[[Category: Nair, S K.]]

	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Thu Jul 3 14~~:30:~~25 2008~~''		''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 07:56:16 2009''

OCA at 11:30, 3 July 2008

2008-07-03T11:30:25Z

← Older revision		Revision as of 11:30, 3 July 2008
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	[[Image:7ca2.~~gif~~\|left\|200px]]		{{Seed}}
			[[Image:7ca2.png\|left\|200px]]

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	{{STRUCTURE_7ca2\| PDB=7ca2 \| SCENE= }}		{{STRUCTURE_7ca2\| PDB=7ca2 \| SCENE= }}

	~~'''~~ENGINEERING THE HYDROPHOBIC POCKET OF CARBONIC ANHYDRASE II~~'''~~		===ENGINEERING THE HYDROPHOBIC POCKET OF CARBONIC ANHYDRASE II===


	~~==Overview==~~		<!--
	~~Wild-type and mutant human carbonic anhydrases II, where mutations have been made in the hydrophobic pocket of the active site, have been studied by X~~-~~ray crystallographic methods. Specifically, mutations at Val~~-~~143 (the base of the pocket) lead to significant changes in catalytic activity and protein structure.~~ The ~~obliteration of a well-defined pocket in the Val-143----Phe and Val-143----Tyr mutants results in significantly diminished enzyme activity [(5 x 10(4))-fold and (3 x 10(5))-fold~~, ~~respectively]; however~~, the ~~activity of~~ the ~~Val-143----His mutant is diminished less~~ (~~10(2)-fold~~), and deepening the pocket in the Val-143----Gly mutant results in only a 2-fold decrease in activity [Fierke et al., 1991 (preceding paper in this issue)]. These results indicate that the hydrophobic pocket is ~~important for substrate association with the enzyme, but there are probably several catalytically acceptable substrate trajectories through this region of~~ the ~~enzyme structure~~. ~~Additionally, each mutant protein exhibits long~~-~~range (ca. 10~~-15 A) compensatory structural changes which accommodate the Val-143 substitution. As such, the genetic-structural approach represented in this work serves as a three-dimensional paradigm for the redesign of specificity pockets in other protein catalysts.		The line below this paragraph, {{ABSTRACT_PUBMED_1932029}}, adds the Publication Abstract to the page
			(as it appears on PubMed at http://www.pubmed.gov), where 1932029 is the PubMed ID number.
			-->
			{{ABSTRACT_PUBMED_1932029}}

	==About this Structure==		==About this Structure==
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	[[Category: Christianson, D W.]]		[[Category: Christianson, D W.]]
	[[Category: Nair, S K.]]		[[Category: Nair, S K.]]
	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sun May~~ ~~4 22~~:44:10 2008''
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