3b4f
From Proteopedia
(New page: 200px<br /><applet load="3b4f" size="350" color="white" frame="true" align="right" spinBox="true" caption="3b4f, resolution 1.89Å" /> '''Carbonic anhydrase i...) |
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==Overview== | ==Overview== | ||
| - | 2-(Hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide was tested for its | + | 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 Structure== | ==About this Structure== | ||
| - | 3B4F 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]. | + | 3B4F 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]. |
==Reference== | ==Reference== | ||
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[[Category: Salman, a.]] | [[Category: Salman, a.]] | ||
[[Category: Scozzafava, A.]] | [[Category: Scozzafava, A.]] | ||
| - | [[Category: Supuran, c | + | [[Category: Supuran, c t.]] |
[[Category: Temperini, c.]] | [[Category: Temperini, c.]] | ||
[[Category: HG]] | [[Category: HG]] | ||
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[[Category: zinc]] | [[Category: zinc]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:03:14 2008'' |
Revision as of 17:03, 21 February 2008
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Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide with twelve mammalian isoforms: kinetic and X-Ray crystallographic studies
Overview
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 Structure
3B4F is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Known structural/functional Sites: , and . Full crystallographic information is available from 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:18024029
Page seeded by OCA on Thu Feb 21 19:03:14 2008
Categories: Carbonate dehydratase | Homo sapiens | Single protein | Guzel, o. | Innocenti, a. | Salman, a. | Scozzafava, A. | Supuran, c t. | Temperini, c. | HG | TUO | ZN | Acetylation | Carbonic anhydrase | Crystal structure | Cytoplasm | Disease mutation | Inhibitors | Lyase | Lyase(oxo-acid) | Metal-binding | Polymorphism | Sulfonamide | Zinc
