2f3f
From Proteopedia
(New page: 200px<br /> <applet load="2f3f" size="450" color="white" frame="true" align="right" spinBox="true" caption="2f3f, resolution 2.300Å" /> '''Crystal Structure ...) |
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| - | [[Image:2f3f.gif|left|200px]]<br /> | + | [[Image:2f3f.gif|left|200px]]<br /><applet load="2f3f" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2f3f, resolution 2.300Å" /> | caption="2f3f, resolution 2.300Å" /> | ||
'''Crystal Structure of the Bace complex with BDF488, a macrocyclic inhibitor'''<br /> | '''Crystal Structure of the Bace complex with BDF488, a macrocyclic inhibitor'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2F3F 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 AXF as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.46 3.4.23.46] Full crystallographic information is available from [http:// | + | 2F3F 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=AXF:'>AXF</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.46 3.4.23.46] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F3F OCA]. |
==Reference== | ==Reference== | ||
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[[Category: memapsin2]] | [[Category: memapsin2]] | ||
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Revision as of 15:24, 15 February 2008
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Crystal Structure of the Bace complex with BDF488, a macrocyclic inhibitor
Overview
Based on the X-ray cocrystal structure of the Tang-Ghosh heptapeptide, inhibitor 1 (OM00-3), a series of macroheterocyclic analogues were, designed and synthesized. Analogues containing dithia, dioxa, oxathia, and, carbathia macrocycles were synthesized by methods relying on ring-closing, olefin metathesis for the dioxa analogues and by alkylation of thiolates, or bisthiolates for the others. Molecular modeling suggested that the, incorporation of piperidine units appended to the macrocycles improved, interactions through additional H-bonds and introduced further rigidity., These were synthesized in enantiomerically pure form using, enzyme-catalyzed desymmetrization and diastereomer separation. Inhibitory, activity on beta-site amyloid precursor protein cleaving enzyme (BACE) was, observed with several macroheterocyclic inhibitors and structure-activity, relationship (SAR) correlations were deduced. Cocrystal structures of two, synthetic analogues revealed interesting and unexpected binding, interactions.
About this Structure
2F3F is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Memapsin 2, with EC number 3.4.23.46 Full crystallographic information is available from OCA.
Reference
Structure-based design and synthesis of macroheterocyclic peptidomimetic inhibitors of the aspartic protease beta-site amyloid precursor protein cleaving enzyme (BACE)., Hanessian S, Yang G, Rondeau JM, Neumann U, Betschart C, Tintelnot-Blomley M, J Med Chem. 2006 Jul 27;49(15):4544-67. PMID:16854060
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