2h15: Difference between revisions

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[[Image:2h15.~~gif~~|left|200px]]

[[Image:2h15.png|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~~'''~~

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

~~==Overview==~~

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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.~~

The line below this paragraph, {{ABSTRACT_PUBMED_17125255}}, adds the Publication Abstract to the page

(as it appears on PubMed at http://www.pubmed.gov), where 17125255 is the PubMed ID number.

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==About this Structure==

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[[Category: Crystal structure]]

[[Category: Inhibitor]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sun May 4 05~~:44:47 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 13:30:13 2008''

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-[[Image:2h15.gif|left|200px]]
+{{Seed}}
+[[Image:2h15.png|left|200px]]
 <!--
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 {{STRUCTURE_2h15|  PDB=2h15  |  SCENE=  }}
-'''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===
-==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.
+The line below this paragraph, {{ABSTRACT_PUBMED_17125255}}, adds the Publication Abstract to the page
+(as it appears on PubMed at http://www.pubmed.gov), where 17125255 is the PubMed ID number.
+-->
+{{ABSTRACT_PUBMED_17125255}}
 ==About this Structure==
@@ Line 31: / Line 35: @@
 [[Category: Crystal structure]]
 [[Category: Inhibitor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 05:44:47 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 13:30:13 2008''