5u0d: Difference between revisions

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-'''Unreleased structure'''
-The entry 5u0d is ON HOLD
+==Identification of a New Zinc Binding Chemotype by Fragment Screening==
+<StructureSection load='5u0d' size='340' side='right'caption='[[5u0d]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5u0d]] 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=5U0D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U0D 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]] 1.59&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7R7:(5R)-5-(2,4-dimethoxyphenyl)-2-sulfanylidene-1,3-oxazolidin-4-one'>7R7</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5u0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u0d OCA], [https://pdbe.org/5u0d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u0d RCSB], [https://www.ebi.ac.uk/pdbsum/5u0d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u0d 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 discovery of a new zinc binding chemotype from screening a non-biased fragment library is reported. Using the orthogonal fragment screening methods of native state mass spectrometry and surface plasmon resonance a 3-unsubstituted-2,4-oxazolidinedione fragment was found to have low micromolar binding affinity to the zinc metalloenzyme carbonic anhydrase II (CA II). This affinity approached that of fragment sized primary benzene sulfonamides, the classical zinc binding group found in most CA II inhibitors. Protein X-ray crystallography established that 3-unsubstituted-2,4-oxazolidinediones bound to CA II via an interaction of the acidic ring nitrogen with the CA II active site zinc, as well as a hydrogen bond between the oxazolidinedione ring oxygen and the CA II protein backbone. Furthermore, 3-unsubstituted-2,4-oxazolidinediones appear to be a viable starting point for the development of an alternative class of CA inhibitor, wherein the medicinal chemistry pedigree of primary sulfonamides has dominated for several decades.
-Authors: Peat, T.S., Poulsen, S.A., Ren, B., Dolezal, O., Woods, L.A., Mujumdar, P., Chrysanthopoulos, P.K.
+Identification of a New Zinc Binding Chemotype by Fragment Screening.,Chrysanthopoulos PK, Mujumdar P, Woods LA, Dolezal O, Ren B, Peat TS, Poulsen SA J Med Chem. 2017 Aug 17. doi: 10.1021/acs.jmedchem.7b00606. PMID:28817930<ref>PMID:28817930</ref>
-Description: Identification of a New Zinc Binding Chemotype by Fragment Screening
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Poulsen, S.A]]
+<div class="pdbe-citations 5u0d" style="background-color:#fffaf0;"></div>
-[[Category: Peat, T.S]]
-[[Category: Chrysanthopoulos, P.K]]
+==See Also==
-[[Category: Mujumdar, P]]
+*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
-[[Category: Woods, L.A]]
+== References ==
-[[Category: Ren, B]]
+<references/>
-[[Category: Dolezal, O]]
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Chrysanthopoulos PK]]
+[[Category: Dolezal O]]
+[[Category: Mujumdar P]]
+[[Category: Peat TS]]
+[[Category: Poulsen SA]]
+[[Category: Ren B]]
+[[Category: Woods LA]]