View source for 4zwz


==Engineered Carbonic Anhydrase IX mimic in complex with a glucosyl sulfamate inhibitor==
<StructureSection load='4zwz' size='340' side='right'caption='[[4zwz]], [[Resolution|resolution]] 1.62&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4zwz]] 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=4ZWZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZWZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.62&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=510:METHYL+(2S,4R)-1-[(2S,3R,4R,5S,6S)-6-(HYDROXYMETHYL)-3,4,5-TRIS(OXIDANYL)OXAN-2-YL]SULFONYL-4-SULFAMOYLOXY-PYRROLIDINE-2-CARBOXYLATE'>510</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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'>[https://proteopedia.org/fgij/fg.htm?mol=4zwz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zwz OCA], [https://pdbe.org/4zwz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zwz RCSB], [https://www.ebi.ac.uk/pdbsum/4zwz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zwz 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 ==
Inhibition of human carbonic anhydrase IX (hCA IX) has shown to be therapeutically advantageous for treating many types of highly aggressive cancers. However, designing selective inhibitors for hCA IX has been difficult due to its high structural homology and sequence similarity with off-target hCAs. Recently the use of glucosyl sulfamate inhibitors has shown promise as selective inhibitors for hCA IX. In this study we present five X-ray crystal structures, determined to a resolution of 1.7 A or better, of both hCA II (a ubiquitous CA) and an engineered hCA IX-mimic in complex with selected glucosyl sulfamates and structurally rationalize mechanisms for hCA IX selectivity. Results from this study have allowed us, for the first time, to empirically "map" key interactions of the hCA IX active site in order to establish parameters needed to design novel hCA IX selective inhibitors.

Mapping Selective Inhibition of the Cancer-Related Carbonic Anhydrase IX using Structure-Activity Relationships of Glucosyl-Based Sulfamates.,Mahon BP, Lomelino CL, Ladwig J, Rankin GM, Driscoll JM, Salguero AL, Pinard MA, Vullo D, Supuran CT, Poulsen SA, McKenna R J Med Chem. 2015 Jul 23. PMID:26203869<ref>PMID:26203869</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4zwz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Driscoll JM]]
[[Category: Lomelino CL]]
[[Category: Mahon BP]]
[[Category: McKenna R]]