2pow
From Proteopedia
(New page: 200px<br /> <applet load="2pow" size="450" color="white" frame="true" align="right" spinBox="true" caption="2pow, resolution 1.75Å" /> '''The crystal structu...) |
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| - | [[Image:2pow.gif|left|200px]]<br /> | + | [[Image:2pow.gif|left|200px]]<br /><applet load="2pow" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2pow, resolution 1.75Å" /> | caption="2pow, resolution 1.75Å" /> | ||
'''The crystal structure of the human carbonic anhydrase II in complex with 4-amino-6-trifluoromethyl-benzene-1,3-disulfonamide'''<br /> | '''The crystal structure of the human carbonic anhydrase II in complex with 4-amino-6-trifluoromethyl-benzene-1,3-disulfonamide'''<br /> | ||
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==Overview== | ==Overview== | ||
Three benzene-1,3-disulfonamide derivatives were investigated for their, interaction with 12 mammalian alpha-carbonic anhydrases (CAs, EC 4.2.1.1), and three bacterial/archaeal CAs belonging to the alpha-, beta-, and, gamma-CA class, respectively. X-ray crystal structure of the three, inhibitors in complex with the dominant human isozyme CA II revealed a, particular binding mode within the cavity. The sulfonamide group in, meta-position to the Zn(2+)-coordinated SO(2)NH(2) moiety was oriented, toward the hydrophilic side of the active site cleft, establishing, hydrogen bonds with His64, Asn67, Gln92, and Thr200. The plane of the, phenyl moiety of the inhibitors was rotated by 45 degrees and tilted by 10, degrees with respect to its most recurrent orientation in other CA, II-sulfonamide complexes. | Three benzene-1,3-disulfonamide derivatives were investigated for their, interaction with 12 mammalian alpha-carbonic anhydrases (CAs, EC 4.2.1.1), and three bacterial/archaeal CAs belonging to the alpha-, beta-, and, gamma-CA class, respectively. X-ray crystal structure of the three, inhibitors in complex with the dominant human isozyme CA II revealed a, particular binding mode within the cavity. The sulfonamide group in, meta-position to the Zn(2+)-coordinated SO(2)NH(2) moiety was oriented, toward the hydrophilic side of the active site cleft, establishing, hydrogen bonds with His64, Asn67, Gln92, and Thr200. The plane of the, phenyl moiety of the inhibitors was rotated by 45 degrees and tilted by 10, degrees with respect to its most recurrent orientation in other CA, II-sulfonamide complexes. | ||
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| - | ==Disease== | ||
| - | Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611492 611492]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2POW 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 and I7C 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:// | + | 2POW 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> and <scene name='pdbligand=I7C:'>I7C</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=2POW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: protein-inhibitor complexes]] | [[Category: protein-inhibitor complexes]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:26:27 2008'' |
Revision as of 12:26, 23 January 2008
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The crystal structure of the human carbonic anhydrase II in complex with 4-amino-6-trifluoromethyl-benzene-1,3-disulfonamide
Overview
Three benzene-1,3-disulfonamide derivatives were investigated for their, interaction with 12 mammalian alpha-carbonic anhydrases (CAs, EC 4.2.1.1), and three bacterial/archaeal CAs belonging to the alpha-, beta-, and, gamma-CA class, respectively. X-ray crystal structure of the three, inhibitors in complex with the dominant human isozyme CA II revealed a, particular binding mode within the cavity. The sulfonamide group in, meta-position to the Zn(2+)-coordinated SO(2)NH(2) moiety was oriented, toward the hydrophilic side of the active site cleft, establishing, hydrogen bonds with His64, Asn67, Gln92, and Thr200. The plane of the, phenyl moiety of the inhibitors was rotated by 45 degrees and tilted by 10, degrees with respect to its most recurrent orientation in other CA, II-sulfonamide complexes.
About this Structure
2POW 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.
Reference
Carbonic anhydrase inhibitors: Inhibition of human, bacterial, and archaeal isozymes with benzene-1,3-disulfonamides-Solution and crystallographic studies., Alterio V, De Simone G, Monti SM, Scozzafava A, Supuran CT, Bioorg Med Chem Lett. 2007 Aug 1;17(15):4201-7. Epub 2007 May 18. PMID:17540563
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