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| | ==Design, Synthesis, X-ray and Biological Activities of Selenides Bearing the Benzenesulfonamide Moiety as New Class of Agents for Prevention of Diabetic Cerebrovascular Pathology== | | ==Design, Synthesis, X-ray and Biological Activities of Selenides Bearing the Benzenesulfonamide Moiety as New Class of Agents for Prevention of Diabetic Cerebrovascular Pathology== |
| - | <StructureSection load='6ceh' size='340' side='right' caption='[[6ceh]], [[Resolution|resolution]] 1.43Å' scene=''> | + | <StructureSection load='6ceh' size='340' side='right'caption='[[6ceh]], [[Resolution|resolution]] 1.43Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ceh]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CEH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CEH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ceh]] 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=6CEH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CEH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EZ1:4-[(prop-2-en-1-yl)selanyl]benzene-1-sulfonamide'>EZ1</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.43Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] </span></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EZ1:4-[(prop-2-en-1-yl)selanyl]benzene-1-sulfonamide'>EZ1</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ceh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ceh OCA], [http://pdbe.org/6ceh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ceh RCSB], [http://www.ebi.ac.uk/pdbsum/6ceh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ceh 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=6ceh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ceh OCA], [https://pdbe.org/6ceh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ceh RCSB], [https://www.ebi.ac.uk/pdbsum/6ceh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ceh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN]] Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:[http://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 == |
| - | [[http://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;"> |
| | + | == Publication Abstract from PubMed == |
| | + | A series of novel selenides bearing benzenesulfonamide moieties was synthesized and investigated for their inhibition on six human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms such as the physiologically relevant hCA I, II, VA, VB, VII, and IX and the X-ray complex in adduct with hCA II for some of them investigated. These enzymes are involved in a variety of diseases including glaucoma, retinitis pigmentosa, epilepsy, arthritis, metabolic disorders, and cancer. The investigated compounds showed potent inhibitory action against hCA VA, VII, and IX, in the low nanomolar range, thus making them of interest for the development of isoform-selective inhibitors and as candidates for various biomedical applications. |
| | + | |
| | + | Design, Synthesis, and X-ray of Selenides as New Class of Agents for Prevention of Diabetic Cerebrovascular Pathology.,Angeli A, di Cesare Mannelli L, Trallori E, Peat TS, Ghelardini C, Carta F, Supuran CT ACS Med Chem Lett. 2018 Apr 9;9(5):462-467. doi: 10.1021/acsmedchemlett.8b00076. , eCollection 2018 May 10. PMID:29795760<ref>PMID:29795760</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 6ceh" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Carbonate dehydratase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Angeli, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Carta, F]] | + | [[Category: Angeli A]] |
| - | [[Category: Ghelardini, C]] | + | [[Category: Carta F]] |
| - | [[Category: Mannelli, L di Cesare]] | + | [[Category: Ghelardini C]] |
| - | [[Category: Peat, T S]] | + | [[Category: Peat TS]] |
| - | [[Category: Supuran, C T]] | + | [[Category: Supuran CT]] |
| - | [[Category: Trallori, E]] | + | [[Category: Trallori E]] |
| - | [[Category: Carbonic anhydrase inhibitor]] | + | [[Category: Di Cesare Mannelli L]] |
| - | [[Category: Diabetic pathology]]
| + | |
| - | [[Category: Lyase-lyase inhibitor complex]]
| + | |
| - | [[Category: Organoselenium]]
| + | |
| Structural highlights
Disease
CAH2_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]
Function
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.[6] [7]
Publication Abstract from PubMed
A series of novel selenides bearing benzenesulfonamide moieties was synthesized and investigated for their inhibition on six human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms such as the physiologically relevant hCA I, II, VA, VB, VII, and IX and the X-ray complex in adduct with hCA II for some of them investigated. These enzymes are involved in a variety of diseases including glaucoma, retinitis pigmentosa, epilepsy, arthritis, metabolic disorders, and cancer. The investigated compounds showed potent inhibitory action against hCA VA, VII, and IX, in the low nanomolar range, thus making them of interest for the development of isoform-selective inhibitors and as candidates for various biomedical applications.
Design, Synthesis, and X-ray of Selenides as New Class of Agents for Prevention of Diabetic Cerebrovascular Pathology.,Angeli A, di Cesare Mannelli L, Trallori E, Peat TS, Ghelardini C, Carta F, Supuran CT ACS Med Chem Lett. 2018 Apr 9;9(5):462-467. doi: 10.1021/acsmedchemlett.8b00076. , eCollection 2018 May 10. PMID:29795760[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Venta PJ, Welty RJ, Johnson TM, Sly WS, Tashian RE. Carbonic anhydrase II deficiency syndrome in a Belgian family is caused by a point mutation at an invariant histidine residue (107 His----Tyr): complete structure of the normal human CA II gene. Am J Hum Genet. 1991 Nov;49(5):1082-90. PMID:1928091
- ↑ Roth DE, Venta PJ, Tashian RE, Sly WS. Molecular basis of human carbonic anhydrase II deficiency. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1804-8. PMID:1542674
- ↑ Soda H, Yukizane S, Yoshida I, Koga Y, Aramaki S, Kato H. A point mutation in exon 3 (His 107-->Tyr) in two unrelated Japanese patients with carbonic anhydrase II deficiency with central nervous system involvement. Hum Genet. 1996 Apr;97(4):435-7. PMID:8834238
- ↑ Hu PY, Lim EJ, Ciccolella J, Strisciuglio P, Sly WS. Seven novel mutations in carbonic anhydrase II deficiency syndrome identified by SSCP and direct sequencing analysis. Hum Mutat. 1997;9(5):383-7. PMID:9143915 doi:<383::AID-HUMU1>3.0.CO;2-5 10.1002/(SICI)1098-1004(1997)9:5<383::AID-HUMU1>3.0.CO;2-5
- ↑ Shah GN, Bonapace G, Hu PY, Strisciuglio P, Sly WS. Carbonic anhydrase II deficiency syndrome (osteopetrosis with renal tubular acidosis and brain calcification): novel mutations in CA2 identified by direct sequencing expand the opportunity for genotype-phenotype correlation. Hum Mutat. 2004 Sep;24(3):272. PMID:15300855 doi:10.1002/humu.9266
- ↑ Briganti F, Mangani S, Scozzafava A, Vernaglione G, Supuran CT. Carbonic anhydrase catalyzes cyanamide hydration to urea: is it mimicking the physiological reaction? J Biol Inorg Chem. 1999 Oct;4(5):528-36. PMID:10550681
- ↑ Kim CY, Whittington DA, Chang JS, Liao J, May JA, Christianson DW. Structural aspects of isozyme selectivity in the binding of inhibitors to carbonic anhydrases II and IV. J Med Chem. 2002 Feb 14;45(4):888-93. PMID:11831900
- ↑ Angeli A, di Cesare Mannelli L, Trallori E, Peat TS, Ghelardini C, Carta F, Supuran CT. Design, Synthesis, and X-ray of Selenides as New Class of Agents for Prevention of Diabetic Cerebrovascular Pathology. ACS Med Chem Lett. 2018 Apr 9;9(5):462-467. doi: 10.1021/acsmedchemlett.8b00076. , eCollection 2018 May 10. PMID:29795760 doi:http://dx.doi.org/10.1021/acsmedchemlett.8b00076
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