2h15
From Proteopedia
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| - | [[Image:2h15.gif|left|200px]] | + | [[Image:2h15.gif|left|200px]] |
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| - | '''Carbonic anhydrase inhibitors: Clashing with Ala65 as a means of designing isozyme-selective inhibitors that show low affinity for the ubiquitous isozyme II''' | + | {{Structure |
| + | |PDB= 2h15 |SIZE=350|CAPTION= <scene name='initialview01'>2h15</scene>, resolution 1.90Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene> and <scene name='pdbligand=B19:N-{[(3AS,5AR,8AR,8BS)-2,2,7,7-TETRAMETHYLTETRAHYDRO-3AH-BIS[1,3]DIOXOLO[4,5-B:4',5'-D]PYRAN-3A-YL]METHYL}SULFAMIDE'>B19</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: Clashing with Ala65 as a means of designing isozyme-selective inhibitors that show low affinity for the ubiquitous isozyme II''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2H15 is a [ | + | 2H15 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=2H15 OCA]. |
==Reference== | ==Reference== | ||
| - | Carbonic anhydrase inhibitors: clash with Ala65 as a means for designing inhibitors with low affinity for the ubiquitous isozyme II, exemplified by the crystal structure of the topiramate sulfamide analogue., Winum JY, Temperini C, El Cheikh K, Innocenti A, Vullo D, Ciattini S, Montero JL, Scozzafava A, Supuran CT, J Med Chem. 2006 Nov 30;49(24):7024-31. PMID:[http:// | + | Carbonic anhydrase inhibitors: clash with Ala65 as a means for designing inhibitors with low affinity for the ubiquitous isozyme II, exemplified by the crystal structure of the topiramate sulfamide analogue., Winum JY, Temperini C, El Cheikh K, Innocenti A, Vullo D, Ciattini S, Montero JL, Scozzafava A, Supuran CT, J Med Chem. 2006 Nov 30;49(24):7024-31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17125255 17125255] |
[[Category: Carbonate dehydratase]] | [[Category: Carbonate dehydratase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: carbonic anhydrase]] | [[Category: carbonic anhydrase]] | ||
[[Category: crystal structure]] | [[Category: crystal structure]] | ||
| - | [[Category: | + | [[Category: inhibitor]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:11:18 2008'' |
Revision as of 15:11, 20 March 2008
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| , resolution 1.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Activity: | Carbonate dehydratase, with EC number 4.2.1.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Carbonic anhydrase inhibitors: Clashing with Ala65 as a means of designing isozyme-selective inhibitors that show low affinity for the ubiquitous isozyme II
Contents |
Overview
The sulfamide analogue of the antiepileptic drug topiramate is a 210 times less potent inhibitor of isozyme II of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1) compared to topiramate but effectively inhibits isozymes CA VA, VB, VII, XIII, and XIV (KI in the range of 21-35 nM). Its weak binding to CA II is due to a clash between one methyl group of the inhibitor and Ala65 and may be exploited for the drug design of compounds with lower affinity for this ubiquitous isozyme, as Ala65 is unique to CA II. As shown by X-ray crystallography, the sulfamide analogue binds to CA II with the deprotonated sulfamide moiety coordinated to Zn(II) and with the organic scaffold making an extended network of hydrogen bonds with Thr199, Gln92, His94, Asn62, and Thr200. Its binding to this isozyme is more similar to that of topiramate and quite different from that of the topiramate cyclic sulfate analogue RWJ-37947.
Disease
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]
About this Structure
2H15 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Carbonic anhydrase inhibitors: clash with Ala65 as a means for designing inhibitors with low affinity for the ubiquitous isozyme II, exemplified by the crystal structure of the topiramate sulfamide analogue., Winum JY, Temperini C, El Cheikh K, Innocenti A, Vullo D, Ciattini S, Montero JL, Scozzafava A, Supuran CT, J Med Chem. 2006 Nov 30;49(24):7024-31. PMID:17125255
Page seeded by OCA on Thu Mar 20 17:11:18 2008
