1bn3: Difference between revisions

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-[[Image:1bn3.gif|left|200px]]<br />
-<applet load="1bn3" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1bn3, resolution 2.2&Aring;" />
-'''CARBONIC ANHYDRASE II INHIBITOR'''<br />
-==Overview==
+==CARBONIC ANHYDRASE II INHIBITOR==
-X-ray crystal structures of carbonic anhydrase II (CAII) complexed with, sulfonamide inhibitors illuminate the structural determinants of high, affinity binding in the nanomolar regime. The primary binding interaction, is the coordination of a primary sulfonamide group to the active site zinc, ion. Secondary interactions fine-tune tight binding in regions of the, active site cavity &gt;5 A away from zinc, and this work highlights three, such features: (1) advantageous conformational restraints of a bicyclic, thienothiazene-6-sulfonamide-1,1-dioxide inhibitor skeleton in comparison, with a monocyclic 2,5-thiophenedisulfonamide skeleton; (2) optimal, substituents attached to a secondary sulfonamide group targeted to, interact with hydrophobic patches defined by Phe131, Leu198, and Pro202;, and (3) optimal stereochemistry and configuration at the C-4 position of, bicyclic thienothiazene-6-sulfonamides; the C-4 substituent can interact, with His64, the catalytic proton shuttle. Structure-activity relationships, rationalize affinity trends observed during the development of, brinzolamide (Azopt), the newest carbonic anhydrase inhibitor approved for, the treatment of glaucoma.
+<StructureSection load='1bn3' size='340' side='right'caption='[[1bn3]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1bn3]] 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=1BN3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BN3 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]] 2.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AL6:2-(3-METHOXYPHENYL)-2H-THIENO-[3,2-E]-1,2-THIAZINE-6-SULFINAMIDE-1,1-DIOXIDE'>AL6</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</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=1bn3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bn3 OCA], [https://pdbe.org/1bn3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bn3 RCSB], [https://www.ebi.ac.uk/pdbsum/1bn3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bn3 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/bn/1bn3_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=1bn3 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/>
-BN3 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 HG, ZN and AL6 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=1BN3 OCA].
+__TOC__
+</StructureSection>
-==Reference==
-Structural analysis of inhibitor binding to human carbonic anhydrase II., Boriack-Sjodin PA, Zeitlin S, Chen HH, Crenshaw L, Gross S, Dantanarayana A, Delgado P, May JA, Dean T, Christianson DW, Protein Sci. 1998 Dec;7(12):2483-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9865942 9865942]
-[[Category: Carbonate dehydratase]]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Boriack-Sjodin, P.A.]]
+[[Category: Boriack-Sjodin PA]]
-[[Category: Christianson, D.W.]]
+[[Category: Christianson DW]]
-[[Category: Zeitlin, S.]]
+[[Category: Zeitlin S]]
-[[Category: AL6]]
-[[Category: HG]]
-[[Category: ZN]]
-[[Category: co2 hydration]]
-[[Category: lyase]]
-[[Category: zinc enzyme]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:12:17 2007''