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| - | [[Image:1i9m.gif|left|200px]]<br /> | |
| - | <applet load="1i9m" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1i9m, resolution 1.84Å" /> | |
| - | '''CARBONIC ANHYDRASE II (F131V) COMPLEXED WITH 4-(AMINOSULFONYL)-N-[(2,4-DIFLUOROPHENYL)METHYL]-BENZAMIDE'''<br /> | |
| | | | |
| - | ==Overview== | + | ==CARBONIC ANHYDRASE II (F131V) COMPLEXED WITH 4-(AMINOSULFONYL)-N-[(2,4-DIFLUOROPHENYL)METHYL]-BENZAMIDE== |
| - | Intermolecular interactions of eleven different fluoroaromatic inhibitors, are probed within the scaffolding of the crystal lattice of Phe-131-->Val, carbonic anhydrase II. The degree and pattern of fluorine substitution on, the inhibitor benzyl ring modulate its size, shape, and electronic, character. In turn, these properties affect the geometry of intermolecular, interactions between the fluoroaromatic rings of two different inhibitor, molecules bound in the crystal lattice, as determined by X-ray, crystallography. Depending on the degree and pattern of fluorine, substitution, we observe a face-to-face (aromatic-aromatic) interaction, an atom-to-face (carbonyl-aromatic) interaction, or no interaction at all., These interaction geometries are analyzed with regard to van der Waals, electrostatic, and possible charge-transfer effects. For the, aromatic-aromatic interactions investigated in this study, with aromatic, ring quadrupoles specifically "tuned" by the degree and pattern of, fluorination, the structural results suggest that London forces and, charge-transfer complexation dominate over weakly polar electrostatic, interactions in the association of aromatic ring pairs.
| + | <StructureSection load='1i9m' size='340' side='right'caption='[[1i9m]], [[Resolution|resolution]] 1.84Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1i9m]] 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=1I9M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1I9M 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]] 1.84Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=INW:4-(AMINOSULFONYL)-N-[(2,4-DIFLUOROPHENYL)METHYL]-BENZAMIDE'>INW</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=1i9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i9m OCA], [https://pdbe.org/1i9m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1i9m RCSB], [https://www.ebi.ac.uk/pdbsum/1i9m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1i9m 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> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i9/1i9m_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1i9m ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | ==Disease== | + | ==See Also== |
| - | Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611492 611492]]
| + | *[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]] |
| - | | + | == References == |
| - | ==About this Structure== | + | <references/> |
| - | 1I9M is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, HG and INW as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1I9M OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Reference==
| + | |
| - | Fluoroaromatic-fluoroaromatic interactions between inhibitors bound in the crystal lattice of human carbonic anhydrase II., Kim CY, Chandra PP, Jain A, Christianson DW, J Am Chem Soc. 2001 Oct 3;123(39):9620-7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11572683 11572683]
| + | |
| - | [[Category: Carbonate dehydratase]]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Chandra, P.P.]] | + | [[Category: Chandra PP]] |
| - | [[Category: Christianson, D.W.]] | + | [[Category: Christianson DW]] |
| - | [[Category: Jain, A.]] | + | [[Category: Jain A]] |
| - | [[Category: Kim, C.Y.]] | + | [[Category: Kim C-Y]] |
| - | [[Category: HG]]
| + | |
| - | [[Category: INW]]
| + | |
| - | [[Category: ZN]]
| + | |
| - | [[Category: 4-(aminosulfonyl)-n-[(2]]
| + | |
| - | [[Category: 4-difluorophenyl)methyl]-benzamide]]
| + | |
| - | [[Category: human carbonic anhydrase ii]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:27:44 2007''
| + | |
| 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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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
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