2pou: Difference between revisions
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==Overview== | ==Overview== | ||
Three benzene-1,3-disulfonamide derivatives were investigated for their | 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. | ||
==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== | ||
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==Reference== | ==Reference== | ||
Carbonic anhydrase inhibitors: | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17540563 17540563] | ||
[[Category: Carbonate dehydratase]] | [[Category: Carbonate dehydratase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Alterio, V.]] | [[Category: Alterio, V.]] | ||
[[Category: Simone, G | [[Category: Simone, G De.]] | ||
[[Category: I7A]] | [[Category: I7A]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
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[[Category: protein-inhibitor complexes]] | [[Category: protein-inhibitor complexes]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:31:41 2008'' | ||
Revision as of 19:31, 21 February 2008
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The crystal structure of the human carbonic anhydrase II in complex with 4,5-dichloro-benzene-1,3-disulfonamide
OverviewOverview
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.
DiseaseDisease
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]
About this StructureAbout this Structure
2POU 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: 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
Page seeded by OCA on Thu Feb 21 18:31:41 2008