3bl0
From Proteopedia
(New page: 200px<br /><applet load="3bl0" size="350" color="white" frame="true" align="right" spinBox="true" caption="3bl0, resolution 1.90Å" /> '''Carbonic anhydrase i...) |
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==Overview== | ==Overview== | ||
| - | 2-N,N-Dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide was tested for | + | 2-N,N-Dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide was tested for its interaction with the 12 catalytically active mammalian carbonic anhydrase (CA, EC 4.2.1.1) isozymes, CA I-XIV. The compound is a potent inhibitor of CA IV, VII, IX, XII, and XIII (K(I)s of 0.61-39 nM), a medium potency inhibitor of CA II and VA (K(I)s of 121-438 nM), and a weak inhibitor against the other isoforms (CA III, VB, VI, and XIV), making it a very interesting candidate for situations in which a strong/selective inhibition of certain isozymes is needed. The crystal structure of the hCA II adduct of this sulfonamide revealed interesting interactions between the inhibitor and the enzyme which are quite different from those observed in the adducts of CA II with the structurally related aliphatic derivatives zonisamide, 2-amino-1,3,4-thiadiazolyl-5-difluoromethanesulfonamide, and 2-dimethylamino-5-[sulfonamido-(aminomethyl)]-1,3,4-thiadiazole reported earlier. |
==About this Structure== | ==About this Structure== | ||
| - | 3BL0 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=BL0:'>BL0</scene> and <scene name='pdbligand=MBO:'>MBO</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:Bl0 Binding Site For Residue A 300'>AC2</scene> and <scene name='pdbsite=AC3:Mbo Binding Site For Residue A 301'>AC3</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BL0 OCA]. | + | 3BL0 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=BL0:'>BL0</scene> and <scene name='pdbligand=MBO:'>MBO</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:Bl0+Binding+Site+For+Residue+A+300'>AC2</scene> and <scene name='pdbsite=AC3:Mbo+Binding+Site+For+Residue+A+301'>AC3</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BL0 OCA]. |
==Reference== | ==Reference== | ||
| - | Carbonic anhydrase inhibitors. Interaction of 2-N,N-dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide with 12 mammalian isoforms: | + | Carbonic anhydrase inhibitors. Interaction of 2-N,N-dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide with 12 mammalian isoforms: kinetic and X-ray crystallographic studies., Temperini C, Cecchi A, Boyle NA, Scozzafava A, Cabeza JE, Wentworth P Jr, Blackburn GM, Supuran CT, Bioorg Med Chem Lett. 2008 Feb 1;18(3):999-1005. Epub 2007 Dec 15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18162396 18162396] |
[[Category: Carbonate dehydratase]] | [[Category: Carbonate dehydratase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Blackburn, G | + | [[Category: Blackburn, G M.]] |
| - | [[Category: Supuran, C | + | [[Category: Supuran, C T.]] |
[[Category: Temperini, C.]] | [[Category: Temperini, C.]] | ||
[[Category: BL0]] | [[Category: BL0]] | ||
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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 19:06:23 2008'' |
Revision as of 17:06, 21 February 2008
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Carbonic anhydrase inhibitors. Interaction of 2-N,N-Dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide with twelve mammalian isoforms: kinetic and X-Ray crystallographic studies
Overview
2-N,N-Dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide was tested for its interaction with the 12 catalytically active mammalian carbonic anhydrase (CA, EC 4.2.1.1) isozymes, CA I-XIV. The compound is a potent inhibitor of CA IV, VII, IX, XII, and XIII (K(I)s of 0.61-39 nM), a medium potency inhibitor of CA II and VA (K(I)s of 121-438 nM), and a weak inhibitor against the other isoforms (CA III, VB, VI, and XIV), making it a very interesting candidate for situations in which a strong/selective inhibition of certain isozymes is needed. The crystal structure of the hCA II adduct of this sulfonamide revealed interesting interactions between the inhibitor and the enzyme which are quite different from those observed in the adducts of CA II with the structurally related aliphatic derivatives zonisamide, 2-amino-1,3,4-thiadiazolyl-5-difluoromethanesulfonamide, and 2-dimethylamino-5-[sulfonamido-(aminomethyl)]-1,3,4-thiadiazole reported earlier.
About this Structure
3BL0 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-N,N-dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide with 12 mammalian isoforms: kinetic and X-ray crystallographic studies., Temperini C, Cecchi A, Boyle NA, Scozzafava A, Cabeza JE, Wentworth P Jr, Blackburn GM, Supuran CT, Bioorg Med Chem Lett. 2008 Feb 1;18(3):999-1005. Epub 2007 Dec 15. PMID:18162396
Page seeded by OCA on Thu Feb 21 19:06:23 2008
Categories: Carbonate dehydratase | Homo sapiens | Single protein | Blackburn, G M. | Supuran, C T. | Temperini, C. | BL0 | MBO | ZN | Acetylation | Carbonic anhydrase | Crystal structure | Cytoplasm | Disease mutation | Inhibitors | Lyase | Lyase(oxo-acid) | Metal-binding | Polymorphism | Sulfonamide | Zinc
