3b4f: Difference between revisions

Revision as of 20:23, 4 May 2008

Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide with twelve mammalian isoforms: kinetic and X-Ray crystallographic studies

OverviewOverview

2-(Hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide was tested for its interaction with 12 carbonic anhydrase (CA, EC 4.2.1.1) isoforms in the search of compounds with good inhibitory activity against isozymes with medicinal chemistry applications, such as CA I, II, VA, VB, VII, IX, and XII among others. This sulfonamide is a potent inhibitor of CA I and II (K(I)s of 7.2-7.5 nM), a medium potency inhibitor of CA VII, IX, XII, and XIV, and a weak inhibitor against the other ubiquitous isoforms, making it thus a very interesting clinical candidate for situations in which a strong inhibition of CA I and II is needed. The crystal structure of the hCA II adduct of this sulfonamide revealed many favorable interactions between the inhibitor and the enzyme which explain its strong low nanomolar affinity for this isoform but may also be exploited for the design of effective inhibitors incorporating bicyclic moieties.

About this StructureAbout this Structure

3B4F is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide with 12 mammalian isoforms: kinetic and X-ray crystallographic studies., Guzel O, Temperini C, Innocenti A, Scozzafava A, Salman A, Supuran CT, Bioorg Med Chem Lett. 2008 Jan 1;18(1):152-8. Epub 2007 Nov 4. PMID:18024029 Page seeded by OCA on Sun May 4 20:23:04 2008

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

OCA

@@ Line 1: / Line 1: @@
 [[Image:3b4f.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 3b4f |SIZE=350|CAPTION= <scene name='initialview01'>3b4f</scene>, resolution 1.89&Aring;
+The line below this paragraph, containing "STRUCTURE_3b4f", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:Zn+Binding+Site+For+Residue+A+262'>AC1</scene>, <scene name='pdbsite=AC2:Hg+Binding+Site+For+Residue+A+263'>AC2</scene> and <scene name='pdbsite=AC3:Tuo+Binding+Site+For+Residue+A+300'>AC3</scene>
+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=TUO:2-(HYDRAZINOCARBONYL)-3-PHENYL-1H-INDOLE-5-SULFONAMIDE'>TUO</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_3b4f|  PDB=3b4f  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3b4f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b4f OCA], [http://www.ebi.ac.uk/pdbsum/3b4f PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3b4f RCSB]</span>
-}}
 '''Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide with twelve mammalian isoforms: kinetic and X-Ray crystallographic studies'''
@@ Line 32: / Line 29: @@
 [[Category: Supuran, c t.]]
 [[Category: Temperini, c.]]
-[[Category: acetylation]]
+[[Category: Acetylation]]
-[[Category: carbonic anhydrase]]
+[[Category: Carbonic anhydrase]]
-[[Category: crystal structure]]
+[[Category: Crystal structure]]
-[[Category: cytoplasm]]
+[[Category: Cytoplasm]]
-[[Category: disease mutation]]
+[[Category: Disease mutation]]
-[[Category: inhibitor]]
+[[Category: Inhibitor]]
-[[Category: lyase]]
+[[Category: Lyase]]
-[[Category: lyase(oxo-acid)]]
+[[Category: Metal-binding]]
-[[Category: metal-binding]]
+[[Category: Polymorphism]]
-[[Category: polymorphism]]
+[[Category: Sulfonamide]]
-[[Category: sulfonamide]]
+[[Category: Zinc]]
-[[Category: zinc]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 20:23:04 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:22:58 2008''