2o4z: Difference between revisions
New page: left|200px<br /> <applet load="2o4z" size="450" color="white" frame="true" align="right" spinBox="true" caption="2o4z, resolution 2.10Å" /> '''Crystal structure o... |
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[[Image:2o4z.gif|left|200px]]<br /> | [[Image:2o4z.gif|left|200px]]<br /><applet load="2o4z" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="2o4z, resolution 2.10Å" /> | caption="2o4z, resolution 2.10Å" /> | ||
'''Crystal structure of the Carbonic Anhydrase II complexed with hydroxysulfamide inhibitor'''<br /> | '''Crystal structure of the Carbonic Anhydrase II complexed with hydroxysulfamide inhibitor'''<br /> | ||
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==Overview== | ==Overview== | ||
N-Hydroxysulfamide is a 2000-fold more potent inhibitor of the zinc enzyme, carbonic anhydrase (CA, EC 4.2.1.1) as compared to sulfamide. It also, inhibits other physiologically relevant isoforms, such as the, tumor-associated CA IX and XII (K(I)s in the range of 0.865-1.34muM). In, order to understand the binding of this inhibitor to the enzyme active, site, the X-ray crystal structure of the human hCA II-N-hydroxysulfamide, adduct was resolved. The inhibitor coordinates to the active site zinc ion, by the ionized primary amino group, participating in an extended network, of hydrogen bonds with amino acid residues Thr199, Thr200 and two water, molecules. The additional two hydrogen bonds in which N-hydroxysulfamide, bound to hCA II is involved as compared to the corresponding adduct of, sulfamide may explain its higher affinity for the enzyme, also providing, hints for the design of tight-binding CA inhibitors possessing an organic, moiety substituting the NH group in the N-hydroxysulfamide structure. | N-Hydroxysulfamide is a 2000-fold more potent inhibitor of the zinc enzyme, carbonic anhydrase (CA, EC 4.2.1.1) as compared to sulfamide. It also, inhibits other physiologically relevant isoforms, such as the, tumor-associated CA IX and XII (K(I)s in the range of 0.865-1.34muM). In, order to understand the binding of this inhibitor to the enzyme active, site, the X-ray crystal structure of the human hCA II-N-hydroxysulfamide, adduct was resolved. The inhibitor coordinates to the active site zinc ion, by the ionized primary amino group, participating in an extended network, of hydrogen bonds with amino acid residues Thr199, Thr200 and two water, molecules. The additional two hydrogen bonds in which N-hydroxysulfamide, bound to hCA II is involved as compared to the corresponding adduct of, sulfamide may explain its higher affinity for the enzyme, also providing, hints for the design of tight-binding CA inhibitors possessing an organic, moiety substituting the NH group in the N-hydroxysulfamide structure. | ||
==About this Structure== | ==About this Structure== | ||
2O4Z 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 ZN, HG and HSW 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] Full crystallographic information is available from [http:// | 2O4Z 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=HSW:'>HSW</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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O4Z OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: inhibitors]] | [[Category: inhibitors]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:16:49 2008'' | ||
Revision as of 16:16, 23 January 2008
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Crystal structure of the Carbonic Anhydrase II complexed with hydroxysulfamide inhibitor
OverviewOverview
N-Hydroxysulfamide is a 2000-fold more potent inhibitor of the zinc enzyme, carbonic anhydrase (CA, EC 4.2.1.1) as compared to sulfamide. It also, inhibits other physiologically relevant isoforms, such as the, tumor-associated CA IX and XII (K(I)s in the range of 0.865-1.34muM). In, order to understand the binding of this inhibitor to the enzyme active, site, the X-ray crystal structure of the human hCA II-N-hydroxysulfamide, adduct was resolved. The inhibitor coordinates to the active site zinc ion, by the ionized primary amino group, participating in an extended network, of hydrogen bonds with amino acid residues Thr199, Thr200 and two water, molecules. The additional two hydrogen bonds in which N-hydroxysulfamide, bound to hCA II is involved as compared to the corresponding adduct of, sulfamide may explain its higher affinity for the enzyme, also providing, hints for the design of tight-binding CA inhibitors possessing an organic, moiety substituting the NH group in the N-hydroxysulfamide structure.
About this StructureAbout this Structure
2O4Z 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 Full crystallographic information is available from OCA.
ReferenceReference
Carbonic anhydrase inhibitors: The X-ray crystal structure of the adduct of N-hydroxysulfamide with isozyme II explains why this new zinc binding function is effective in the design of potent inhibitors., Temperini C, Winum JY, Montero JL, Scozzafava A, Supuran CT, Bioorg Med Chem Lett. 2007 May 15;17(10):2795-801. Epub 2007 Feb 28. PMID:17346964
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