2h15

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[[Image:2h15.gif|left|200px]]
[[Image:2h15.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 2h15 |SIZE=350|CAPTION= <scene name='initialview01'>2h15</scene>, resolution 1.90&Aring;
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The line below this paragraph, containing "STRUCTURE_2h15", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=B19:N-{[(3AS,5AR,8AR,8BS)-2,2,7,7-TETRAMETHYLTETRAHYDRO-3AH-BIS[1,3]DIOXOLO[4,5-B&#58;4&#39;,5&#39;-D]PYRAN-3A-YL]METHYL}SULFAMIDE'>B19</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|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>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=
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{{STRUCTURE_2h15| PDB=2h15 | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2h15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h15 OCA], [http://www.ebi.ac.uk/pdbsum/2h15 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2h15 RCSB]</span>
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}}
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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'''
'''Carbonic anhydrase inhibitors: Clashing with Ala65 as a means of designing isozyme-selective inhibitors that show low affinity for the ubiquitous isozyme II'''
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[[Category: Temperini, C.]]
[[Category: Temperini, C.]]
[[Category: Winum, J Y.]]
[[Category: Winum, J Y.]]
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[[Category: carbonic anhydrase]]
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[[Category: Carbonic anhydrase]]
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[[Category: crystal structure]]
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[[Category: Crystal structure]]
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[[Category: inhibitor]]
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[[Category: Inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:44:47 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:23:59 2008''
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Revision as of 02:44, 4 May 2008

Image:2h15.gif

Template:STRUCTURE 2h15

Carbonic anhydrase inhibitors: Clashing with Ala65 as a means of designing isozyme-selective inhibitors that show low affinity for the ubiquitous isozyme II


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.

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 Sun May 4 05:44:47 2008

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