6ugr: Difference between revisions

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-'''Unreleased structure'''
-The entry 6ugr is ON HOLD
+==Human Carbonic Anhydrase 2 complexed with SB4-208==
+<StructureSection load='6ugr' size='340' side='right'caption='[[6ugr]], [[Resolution|resolution]] 1.31&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6ugr]] 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=6UGR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UGR 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]] 1.307&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=Q71:7-fluoro-1lambda~6~,2,4-benzothiadiazine-1,1,3(2H,4H)-trione'>Q71</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=6ugr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ugr OCA], [https://pdbe.org/6ugr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ugr RCSB], [https://www.ebi.ac.uk/pdbsum/6ugr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ugr 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 ==
+The sweeteners saccharin (SAC) and acesulfame K (ACE) recently entered the topic of anticancer human carbonic anhydrase (CA, EC 4.2.1.1) inhibitors as they showed to selectively inhibit the tumor-associated CAs IX/XII over ubiquitous CAs. A drug design strategy is here reported which took SAC and ACE as leads and produced a series of 2H-benzo[e][1,2,4]thiadiazin-3(4H)-one-1,1-dioxides (BTD). Many derivatives showed greater potency (KIs-CA IX 19.1-408.5 nM) and selectivity (II/IX SI 2-76) than the leads (KIs-CA IX 103, 2400 nM; II/IX-SI 56, &gt;4) against CA IX/XII over off-target isoforms. A thorough X-ray crystallographic study depicted their binding mode to both CA II and IX-mimic. The most representative BTDs were characterized in vitro for their antitumor activity against A549, PC-3 and HCT-116 cancer cell lines both in normoxia and hypoxia. The two most effective compounds were assayed for their effect on several apoptosis markers, identifying promising leads for the development of new anticancer drugs.
-Authors: Murray, A.B., Lomelino, C.L., McKenna, R.
+"A Sweet Combination": Developing saccharin and acesulfame K structures for selectively targeting the tumor-associated carbonic anhydrases IX and XII.,Bua S, Lomelino CL, Murray AB, Osman SM, Alothman ZA, Bozdag M, Aziz HAA, Eldehna WM, McKenna R, Nocentini A, Supuran CT J Med Chem. 2019 Dec 3. doi: 10.1021/acs.jmedchem.9b01669. PMID:31794211<ref>PMID:31794211</ref>
-Description: Human Carbonic Anhydrase 2 complexed with SB4-208
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Lomelino, C.L]]
+<div class="pdbe-citations 6ugr" style="background-color:#fffaf0;"></div>
-[[Category: Mckenna, R]]
-[[Category: Murray, A.B]]
+==See Also==
+*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Lomelino CL]]
+[[Category: McKenna R]]
+[[Category: Murray AB]]