3b4f: Difference between revisions

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Revision as of 19:56, 20 March 2008

File:3b4f.jpg

, resolution 1.89Å

Sites:

, and

Ligands:

, and

Activity:

Carbonate dehydratase, with EC number 4.2.1.1

Coordinates:

save as pdb, mmCIF, xml

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 Thu Mar 20 18:56:02 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]]<br /><applet load="3b4f" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:3b4f.jpg|left|200px]]
-caption="3b4f, resolution 1.89&Aring;" />
-'''Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide with twelve mammalian isoforms: kinetic and X-Ray crystallographic studies'''<br />
+ {{Structure
+|PDB= 3b4f |SIZE=350|CAPTION= <scene name='initialview01'>3b4f</scene>, resolution 1.89&Aring;
+|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>
+|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene> and <scene name='pdbligand=TUO:'>TUO</scene>
+|ACTIVITY= [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]
+|GENE=
+}}
+'''Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide with twelve mammalian isoforms: kinetic and X-Ray crystallographic studies'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-B4F 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> and <scene name='pdbligand=TUO:'>TUO</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 Sites: <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>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B4F OCA].
+B4F is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B4F OCA].
 ==Reference==
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18024029 18024029]
+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:[http://www.ncbi.nlm.nih.gov/pubmed/18024029 18024029]
 [[Category: Carbonate dehydratase]]
 [[Category: Homo sapiens]]
@@ Line 28: / Line 37: @@
 [[Category: cytoplasm]]
 [[Category: disease mutation]]
-[[Category: inhibitors]]
+[[Category: inhibitor]]
 [[Category: lyase]]
 [[Category: lyase(oxo-acid)]]
@@ Line 36: / Line 45: @@
 [[Category: zinc]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:03:14 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:56:02 2008''