1i91: Difference between revisions

Revision as of 19:43, 2 May 2008

CARBONIC ANHYDRASE II COMPLEXED WITH AL-6619 2H-THIENO[3,2-E]-1,2-THIAZINE-6-SULFONAMIDE, 2-(3-HYDROXYPHENYL)-3-(4-MORPHOLINYL)-, 1,1-DIOXIDE

OverviewOverview

Carbonic anhydrase inhibitors are effective in lowering intraocular pressure, the primary indication of glaucoma. Human carbonic anhydrase II, and possibly carbonic anhydrase IV (CAII and CAIV, respectively), help regulate fluid secretion into the anterior chamber of the eye. Because inhibitors currently formulated as drugs to treat glaucoma were designed to target CAII, an understanding of the structural basis of CAII-CAIV discrimination by inhibitors would be useful for probing the role of each isozyme in the etiology of the disease. Here, we report the X-ray crystal structures of three novel thieno[3,2-e]-1,2-thiazine-6-sulfonamides complexed with CAII and the computationally predicted structures of the same compounds complexed with CAIV. All three compounds bind with similar affinity to CAII, but they bind with up to 100-fold lower affinities to CAIV. Comparisons of experimentally determined structures of CAII-inhibitor complexes and computationally predicted structures of CAIV-inhibitor complexes allow us to rationalize these affinity trends and outline molecular features that may contribute to high-affinity inhibitor binding to CAIV. This study demonstrates how experimental structure determination methods and computational structure prediction methods can be used together to answer questions that cannot be answered by either method alone.

About this StructureAbout this Structure

1I91 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Structural aspects of isozyme selectivity in the binding of inhibitors to carbonic anhydrases II and IV., Kim CY, Whittington DA, Chang JS, Liao J, May JA, Christianson DW, J Med Chem. 2002 Feb 14;45(4):888-93. PMID:11831900 Page seeded by OCA on Fri May 2 19:43:20 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1i91.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 1i91 |SIZE=350|CAPTION= <scene name='initialview01'>1i91</scene>, resolution 2.00&Aring;
+The line below this paragraph, containing "STRUCTURE_1i91", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=INQ:6-[N-(3-HYDROXY-PHENYL)-3-(MORPHOLIN-4-YLMETHYL)-2H-THIENO[3,2-E]-1,2-THIAZINE-1,1,-DIOXIDE]-SULFONAMIDE'>INQ</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <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>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1i91|  PDB=1i91  |  SCENE=  }}
-|RELATEDENTRY=[[1i8z|1I8z]], [[1i90|1I90]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1i91 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i91 OCA], [http://www.ebi.ac.uk/pdbsum/1i91 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1i91 RCSB]</span>
-}}
 '''CARBONIC ANHYDRASE II COMPLEXED WITH AL-6619 2H-THIENO[3,2-E]-1,2-THIAZINE-6-SULFONAMIDE, 2-(3-HYDROXYPHENYL)-3-(4-MORPHOLINYL)-, 1,1-DIOXIDE'''
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 [[Category: Liao, J.]]
 [[Category: May, J A.]]
-[[Category: al-6619]]
+[[Category: Al-6619]]
-[[Category: carbonic anhydrase ii]]
+[[Category: Carbonic anhydrase ii]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 19:43:20 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:16:20 2008''