2hl4: Difference between revisions
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New page: left|200px<br /> <applet load="2hl4" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hl4, resolution 1.55Å" /> '''Crystal structure a... |
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[[Image:2hl4.gif|left|200px]]<br /> | [[Image:2hl4.gif|left|200px]]<br /><applet load="2hl4" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2hl4" size=" | |||
caption="2hl4, resolution 1.55Å" /> | caption="2hl4, resolution 1.55Å" /> | ||
'''Crystal structure analysis of human carbonic anhydrase II in complex with a benzenesulfonamide derivative'''<br /> | '''Crystal structure analysis of human carbonic anhydrase II in complex with a benzenesulfonamide derivative'''<br /> | ||
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==Overview== | ==Overview== | ||
N-(4-Sulfamoylphenyl)-alpha-d-glucopyranosylamine, a promising topical, antiglaucoma agent, is a potent inhibitor of the zinc enzyme carbonic, anhydrase (CA, EC 4.2.1.1). The high resolution X-ray crystal structure of, its adduct with the target isoform involved in glaucoma, CA II, is, reported here. The sugar sulfanilamide derivative binds to the enzyme in a, totally new manner as compared to other CA-inhibitor adducts investigated, earlier. The sulfonamide anchor was coordinated to the active site metal, ion, and the phenylene ring of the inhibitor filled the channel leading to, the active site cavity. The glycosyl moiety responsible for the high water, solubility of the compound was oriented towards a hydrophilic region of, the active site, where no other inhibitors were observed to be bound up to, now. A network of seven hydrogen bonds with four water molecules and the, amino acid residues Pro201, Pro202 and Gln92 further stabilize the, enzyme-inhibitor adduct. Topiramate, another sugar-based CA inhibitor, binds in a completely different manner to CA II as compared to the, sulfonamide investigated here. These findings are useful for the design of, potent, sugar-derived enzyme inhibitors. | N-(4-Sulfamoylphenyl)-alpha-d-glucopyranosylamine, a promising topical, antiglaucoma agent, is a potent inhibitor of the zinc enzyme carbonic, anhydrase (CA, EC 4.2.1.1). The high resolution X-ray crystal structure of, its adduct with the target isoform involved in glaucoma, CA II, is, reported here. The sugar sulfanilamide derivative binds to the enzyme in a, totally new manner as compared to other CA-inhibitor adducts investigated, earlier. The sulfonamide anchor was coordinated to the active site metal, ion, and the phenylene ring of the inhibitor filled the channel leading to, the active site cavity. The glycosyl moiety responsible for the high water, solubility of the compound was oriented towards a hydrophilic region of, the active site, where no other inhibitors were observed to be bound up to, now. A network of seven hydrogen bonds with four water molecules and the, amino acid residues Pro201, Pro202 and Gln92 further stabilize the, enzyme-inhibitor adduct. Topiramate, another sugar-based CA inhibitor, binds in a completely different manner to CA II as compared to the, sulfonamide investigated here. These findings are useful for the design of, potent, sugar-derived enzyme inhibitors. | ||
==About this Structure== | ==About this Structure== | ||
2HL4 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, CL, BO1, MBO and GOL 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:// | 2HL4 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=CL:'>CL</scene>, <scene name='pdbligand=BO1:'>BO1</scene>, <scene name='pdbligand=MBO:'>MBO</scene> and <scene name='pdbligand=GOL:'>GOL</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=2HL4 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: protein-inhibitor complex]] | [[Category: protein-inhibitor complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:11:39 2008'' | ||
