View source for 6qfx


==Human carbonic anhydrase II with bound IrCp* complex (cofactor 10) to generate an artificial transfer hydrogenase (ATHase)==
<StructureSection load='6qfx' size='340' side='right'caption='[[6qfx]], [[Resolution|resolution]] 1.32&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6qfx]] 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=6QFX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QFX FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JR3:2-(9-chloranyl-2,3,4,5,6-pentamethyl-4-oxidanyl-7-oxidanylidene-spiro[1$l^{4},8-diaza-9$l^{8}-iridabicyclo[4.3.0]nona-1,3,5-triene-9,1-1$l^{8}-iridapentacyclo[2.2.0.0^{1,3}.0^{1,5}.0^{2,6}]hexane]-8-yl)-~{N}-(4-sulfamoylphenyl)ethanamide'>JR3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CA2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='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=6qfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qfx OCA], [http://pdbe.org/6qfx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qfx RCSB], [http://www.ebi.ac.uk/pdbsum/6qfx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qfx ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN]] Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:[http://omim.org/entry/259730 259730]]; also known as osteopetrosis with renal tubular acidosis, carbonic anhydrase II deficiency syndrome, Guibaud-Vainsel syndrome or marble brain disease. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Autosomal recessive osteopetrosis is usually associated with normal or elevated amount of non-functional osteoclasts. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation.<ref>PMID:1928091</ref> <ref>PMID:1542674</ref> <ref>PMID:8834238</ref> <ref>PMID:9143915</ref> <ref>PMID:15300855</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN]] Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye.<ref>PMID:10550681</ref> <ref>PMID:11831900</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Artificial metalloenzymes combine a synthetic metallocofactor with a protein scaffold and can catalyze abiotic reactions in vivo. Herein, we report on our efforts to valorize human carbonic anhydrase II as a scaffold for whole-cell transfer hydrogenation. Two platforms were tested: periplasmic compartmentalization and surface display in Escherichia coli. A chemical optimization of an IrCp* cofactor was performed. This led to 90 turnovers in the cell, affording a 69-fold increase in periplasmic product formation over the previously reported, sulfonamide-bearing IrCp* cofactor. These findings highlight the versatility of carbonic anhydrase as a promising scaffold for whole-cell catalysis with artificial metalloenzymes.

Chemical Optimization of Whole-Cell Transfer Hydrogenation Using Carbonic Anhydrase as Host Protein.,Rebelein JG, Cotelle Y, Garabedian B, Ward TR ACS Catal. 2019 May 3;9(5):4173-4178. doi: 10.1021/acscatal.9b01006. Epub 2019, Apr 5. PMID:31080690<ref>PMID:31080690</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6qfx" style="background-color:#fffaf0;"></div>

==See Also==
*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Carbonate dehydratase]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Rebelein, J G]]
[[Category: Artificial transfer hydrogenase]]
[[Category: Bound ircp* complex]]
[[Category: Human carbonic anhydrase ii]]
[[Category: Oxidoreductase]]
[[Category: Zinc binding protein]]