View source for 6lv4


==Co- Carbonic Anhydrase II pH 11.0 20 atm CO2==
<StructureSection load='6lv4' size='340' side='right'caption='[[6lv4]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6lv4]] 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=6LV4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LV4 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BCT:BICARBONATE+ION'>BCT</scene>, <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=CO2:CARBON+DIOXIDE'>CO2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6luu|6luu]]</div></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=6lv4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lv4 OCA], [https://pdbe.org/6lv4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lv4 RCSB], [https://www.ebi.ac.uk/pdbsum/6lv4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lv4 ProSAT]</span></td></tr>
</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 ==
Why metalloenzymes often show dramatic changes in their catalytic activity when subjected to chemically similar but non-native metal substitutions is a long-standing puzzle. Here, we report on the catalytic roles of metal ions in a model metalloenzyme system, human carbonic anhydrase II (CA II). Through a comparative study on the intermediate states of the zinc-bound native CA II and non-native metal-substituted CA IIs, we demonstrate that the characteristic metal ion coordination geometries (tetrahedral for Zn(2+), tetrahedral to octahedral conversion for Co(2+), octahedral for Ni(2+), and trigonal bipyramidal for Cu(2+)) directly modulate the catalytic efficacy. In addition, we reveal that the metal ions have a long-range (~10 A) electrostatic effect on restructuring water network in the active site. Our study provides evidence that the metal ions in metalloenzymes have a crucial impact on the catalytic mechanism beyond their primary chemical properties.

Elucidating the role of metal ions in carbonic anhydrase catalysis.,Kim JK, Lee C, Lim SW, Adhikari A, Andring JT, McKenna R, Ghim CM, Kim CU Nat Commun. 2020 Sep 11;11(1):4557. doi: 10.1038/s41467-020-18425-5. PMID:32917908<ref>PMID:32917908</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6lv4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Carbonate dehydratase]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Kim, C U]]
[[Category: Kim, J K]]
[[Category: Biological water dynamic]]
[[Category: Carbonic anhydrase]]
[[Category: Enzyme mechanism]]
[[Category: Lyase]]
[[Category: Metal binding protein]]
[[Category: Metal coordination geometry]]
[[Category: Metalloenzyme]]
[[Category: Proton transfer]]