3hlj: Difference between revisions
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<StructureSection load='3hlj' size='340' side='right'caption='[[3hlj]], [[Resolution|resolution]] 1.44Å' scene=''> | <StructureSection load='3hlj' size='340' side='right'caption='[[3hlj]], [[Resolution|resolution]] 1.44Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3hlj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3hlj]] 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=3HLJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HLJ FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>, <scene name='pdbligand=V21:3-METHYLTHIOBENZIMIDAZO[1,2-C][1,2,3]THIADIAZOL-7-SULFONAMIDE'>V21</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.44Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>, <scene name='pdbligand=V21:3-METHYLTHIOBENZIMIDAZO[1,2-C][1,2,3]THIADIAZOL-7-SULFONAMIDE'>V21</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=3hlj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hlj OCA], [https://pdbe.org/3hlj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hlj RCSB], [https://www.ebi.ac.uk/pdbsum/3hlj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hlj ProSAT]</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=3hlj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hlj OCA], [https://pdbe.org/3hlj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hlj RCSB], [https://www.ebi.ac.uk/pdbsum/3hlj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hlj ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == 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 == | == 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> | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Golovenko | [[Category: Golovenko D]] | ||
[[Category: Grazulis | [[Category: Grazulis S]] | ||
[[Category: Manakova | [[Category: Manakova E]] | ||
Latest revision as of 18:50, 1 November 2023
Crystal structure of human carbonic anhydrase isozyme II with 3-methylthiobenzimidazo[1,2-c][1,2,3]thiadiazol-7-sulfonamideCrystal structure of human carbonic anhydrase isozyme II with 3-methylthiobenzimidazo[1,2-c][1,2,3]thiadiazol-7-sulfonamide
Structural highlights
DiseaseCAH2_HUMAN Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM: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.[1] [2] [3] [4] [5] FunctionCAH2_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.[6] [7] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe binding and inhibition strength of a series of benzimidazo[1,2-c][1,2,3]thiadiazole-7-sulphonamides were determined for recombinant human carbonic anhydrase isoforms I, II, and IX. The inhibition strength was determined by a stop-flow method to measure carbon dioxide hydration. Inhibitor-enzyme binding was determined by two biophysical techniques - isothermal titration calorimetry and thermal shift assay. The co-crystal structure was determined by X-ray crystallography. Comparing the results obtained using three different inhibition and binding methods increased the accuracy of compound affinity ranking and the ability to determine compound inhibitory specificity towards a particular carbonic anhydrase isoform. In most cases, all three methods yielded the same results despite using very different approaches to measure the binding and inhibition reactions. Some of the compounds studied are submicromolar inhibitors of the isoform IX, a prominent cancer target. Inhibition and binding studies of carbonic anhydrase isozymes I, II and IX with benzimidazo[1,2-c][1,2,3]thiadiazole-7-sulphonamides.,Baranauskiene L, Hilvo M, Matuliene J, Golovenko D, Manakova E, Dudutiene V, Michailoviene V, Torresan J, Jachno J, Parkkila S, Maresca A, Supuran CT, Grazulis S, Matulis D J Enzyme Inhib Med Chem. 2010 Feb 18. PMID:20166809[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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