2gd8
From Proteopedia
(New page: 200px<br /> <applet load="2gd8" size="450" color="white" frame="true" align="right" spinBox="true" caption="2gd8, resolution 1.46Å" /> '''Crystal structure a...) |
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caption="2gd8, resolution 1.46Å" /> | caption="2gd8, resolution 1.46Å" /> | ||
'''Crystal structure analysis of the human carbonic anhydrase II in complex with a 2-substituted estradiol bis-sulfamate'''<br /> | '''Crystal structure analysis of the human carbonic anhydrase II in complex with a 2-substituted estradiol bis-sulfamate'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2GD8 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, PO1 and MBO 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:// | + | 2GD8 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=PO1:'>PO1</scene> and <scene name='pdbligand=MBO:'>MBO</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=2GD8 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 Fri Feb 15 17:27:52 2008'' |
Revision as of 15:27, 15 February 2008
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Crystal structure analysis of the human carbonic anhydrase II in complex with a 2-substituted estradiol bis-sulfamate
Contents |
Overview
The anticancer activities and SARs of estradiol-17-O-sulfamates and, estradiol 3,17-O,O-bis-sulfamates (E2bisMATEs) as steroid sulfatase (STS), inhibitors and antiproliferative agents are discussed. Estradiol, 3,17-O,O-bis-sulfamates 20 and 21, in contrast to the 17-O-monosulfamate, 11, proved to be excellent STS inhibitors. 2-Substituted E2bisMATEs 21 and, 23 additionally exhibited potent antiproliferative activity with mean, graph midpoint values of 18-87 nM in the NCI 60-cell-line panel. 21, Exhibited antiangiogenic in vitro and in vivo activity in an early-stage, Lewis lung model, and 23 dosed p.o. caused marked growth inhibition in a, nude mouse xenograft tumor model. Modeling studies suggest that the, E2bisMATEs and 2-MeOE2 share a common mode of binding to tubulin, though, COMPARE analysis of activity profiles was negative. 21 was cocrystallized, with carbonic anhydrase II, and X-ray crystallography revealed unexpected, coordination of the 17-O-sulfamate of 21 to the active site zinc and a, probable additional lower affinity binding site. 2-Substituted E2bisMATEs, are attractive candidates for further development as multitargeted, anticancer agents.
Disease
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]
About this Structure
2GD8 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
2-substituted estradiol bis-sulfamates, multitargeted antitumor agents: synthesis, in vitro SAR, protein crystallography, and in vivo activity., Leese MP, Leblond B, Smith A, Newman SP, Di Fiore A, De Simone G, Supuran CT, Purohit A, Reed MJ, Potter BV, J Med Chem. 2006 Dec 28;49(26):7683-96. PMID:17181151
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