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| <StructureSection load='3s72' size='340' side='right'caption='[[3s72]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='3s72' size='340' side='right'caption='[[3s72]], [[Resolution|resolution]] 1.60Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3s72]] 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=3S72 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S72 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3s72]] 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=3S72 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S72 FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EVE:1H-BENZIMIDAZOLE-2-SULFONAMIDE'>EVE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3s71|3s71]], [[3s73|3s73]], [[3s74|3s74]], [[3s75|3s75]], [[3s76|3s76]], [[3s77|3s77]], [[3s78|3s78]]</div></td></tr>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EVE:1H-BENZIMIDAZOLE-2-SULFONAMIDE'>EVE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=3s72 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s72 OCA], [https://pdbe.org/3s72 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s72 RCSB], [https://www.ebi.ac.uk/pdbsum/3s72 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s72 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=3s72 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s72 OCA], [https://pdbe.org/3s72 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s72 RCSB], [https://www.ebi.ac.uk/pdbsum/3s72 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s72 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>
| | [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>
| | [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;">
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| == Publication Abstract from PubMed ==
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| The hydrophobic effect--a rationalization of the insolubility of nonpolar molecules in water--is centrally important to biomolecular recognition. Despite extensive research devoted to the hydrophobic effect, its molecular mechanisms remain controversial, and there are still no reliably predictive models for its role in protein-ligand binding. Here we describe a particularly well-defined system of protein and ligands--carbonic anhydrase and a series of structurally homologous heterocyclic aromatic sulfonamides--that we use to characterize hydrophobic interactions thermodynamically and structurally. In binding to this structurally rigid protein, a set of ligands (also defined to be structurally rigid) shows the expected gain in binding free energy as hydrophobic surface area is added. Isothermal titration calorimetry demonstrates that enthalpy determines these increases in binding affinity, and that changes in the heat capacity of binding are negative. X-ray crystallography and molecular dynamics simulations are compatible with the proposal that the differences in binding between the homologous ligands stem from changes in the number and organization of water molecules localized in the active site in the bound complexes, rather than (or perhaps in addition to) release of structured water from the apposed hydrophobic surfaces. These results support the hypothesis that structured water molecules--including both the molecules of water displaced by the ligands and those reorganized upon ligand binding--determine the thermodynamics of binding of these ligands at the active site of the protein. Hydrophobic effects in various contexts have different structural and thermodynamic origins, although all may be manifestations of the differences in characteristics of bulk water and water close to hydrophobic surfaces.
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| Mechanism of the hydrophobic effect in the biomolecular recognition of arylsulfonamides by carbonic anhydrase.,Snyder PW, Mecinovic J, Moustakas DT, Thomas SW 3rd, Harder M, Mack ET, Lockett MR, Heroux A, Sherman W, Whitesides GM Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):17889-94. Epub 2011 Oct 19. PMID:22011572<ref>PMID:22011572</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 3s72" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Carbonate dehydratase]] | | [[Category: Homo sapiens]] |
| [[Category: Human]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Heroux, A]] | | [[Category: Heroux A]] |
| [[Category: Snyder, P W]] | | [[Category: Snyder PW]] |
| [[Category: Whitesides, G W]] | | [[Category: Whitesides GW]] |
| [[Category: Alpha beta]]
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| [[Category: Lyase]]
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