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| - | [[Image:1avn.gif|left|200px]]<br /><applet load="1avn" size="350" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1avn, resolution 2.0Å" /> | |
| - | '''HUMAN CARBONIC ANHYDRASE II COMPLEXED WITH THE HISTAMINE ACTIVATOR'''<br /> | |
| | | | |
| - | ==Overview== | + | ==HUMAN CARBONIC ANHYDRASE II COMPLEXED WITH THE HISTAMINE ACTIVATOR== |
| - | The interaction of native and Co(II)-substituted isozymes I and II of, carbonic anhydrase (CA) with histamine, a well-known activator, was, investigated kinetically, spectroscopically, and X-ray, crystallographically. This activator is of the noncompetitive type with, 4-nitrophenyl acetate and CO2 as substrates for both HCA I and HCA II. The, electronic spectrum of the adduct of Co(II)-HCA II with histamine is, similar to the spectrum of the Co(II)-HCA II-phenol adduct, being only, slightly different from that of the uncomplexed enzyme. This is the first, spectroscopic evidence that the activator molecule binds within the active, site, but not directly to the metal ion. X-ray crystallographic data for, the adduct of HCA II with histamine showed that the activator molecule is, bound at the entrance of the active site cavity in a position where it may, actively participate in shuttling protons between the active site and the, bulk solvent. The role of the activators and the reported X-ray crystal, structure of the HCA II-histamine adduct has prompted us to reexamine the, X-ray structures of the different CA isozymes in order to find a, structural basis accounting for their large differences in catalytic rate., A tentative explanation is proposed on the basis of possible pathways of, proton transfer, which constitute the rate-limiting step in the catalytic, reaction.
| + | <StructureSection load='1avn' size='340' side='right'caption='[[1avn]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1avn]] 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=1AVN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AVN 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]] 2Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AZI:AZIDE+ION'>AZI</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=HSM:HISTAMINE'>HSM</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=1avn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1avn OCA], [https://pdbe.org/1avn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1avn RCSB], [https://www.ebi.ac.uk/pdbsum/1avn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1avn 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/av/1avn_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=1avn 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/> |
| - | 1AVN 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 <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=HG:'>HG</scene>, <scene name='pdbligand=AZI:'>AZI</scene> and <scene name='pdbligand=HSM:'>HSM</scene> 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] Known structural/functional Site: <scene name='pdbsite=ZN:Zn+Site'>ZN</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AVN OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Reference==
| + | |
| - | Carbonic anhydrase activators: X-ray crystallographic and spectroscopic investigations for the interaction of isozymes I and II with histamine., Briganti F, Mangani S, Orioli P, Scozzafava A, Vernaglione G, Supuran CT, Biochemistry. 1997 Aug 26;36(34):10384-92. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9265618 9265618]
| + | |
| - | [[Category: Carbonate dehydratase]]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Briganti, F.]] | + | [[Category: Briganti F]] |
| - | [[Category: Mangani, S.]] | + | [[Category: Mangani S]] |
| - | [[Category: Orioli, P.]] | + | [[Category: Orioli P]] |
| - | [[Category: Scozzafava, A.]] | + | [[Category: Scozzafava A]] |
| - | [[Category: Supuran, C.T.]] | + | [[Category: Supuran CT]] |
| - | [[Category: Vernaglione, G.]] | + | [[Category: Vernaglione G]] |
| - | [[Category: AZI]]
| + | |
| - | [[Category: HG]]
| + | |
| - | [[Category: HSM]]
| + | |
| - | [[Category: ZN]]
| + | |
| - | [[Category: lyase]]
| + | |
| - | [[Category: oxo-acid]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:31:46 2008''
| + | |
| 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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