2f3f
From Proteopedia
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|PDB= 2f3f |SIZE=350|CAPTION= <scene name='initialview01'>2f3f</scene>, resolution 2.300Å | |PDB= 2f3f |SIZE=350|CAPTION= <scene name='initialview01'>2f3f</scene>, resolution 2.300Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=AXF:(2R,4S)-N-BUTYL-4-HYDROXY-2-METHYL- 4-((E)-(4AS,12R,15S,17AS)-15-METHYL -14,17-DIOXO-2,3,4,4A,6,9,11,12,13, 14,15,16,17,17A-TETRADECAHYDRO-1H-5 ,10-DITHIA-1,13,16-TRIAZA-BENZOCYCL OPENTADECEN-12-YL)-BUTYRAMIDE'>AXF</scene> | + | |LIGAND= <scene name='pdbligand=AXF:(2R,4S)-N-BUTYL-4-HYDROXY-2-METHYL-+4-((E)-(4AS,12R,15S,17AS)-15-METHYL+-14,17-DIOXO-2,3,4,4A,6,9,11,12,13,+14,15,16,17,17A-TETRADECAHYDRO-1H-5+,10-DITHIA-1,13,16-TRIAZA-BENZOCYCL+OPENTADECEN-12-YL)-BUTYRAMIDE'>AXF</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= BACE1, BACE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= BACE1, BACE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2f3e|2F3E]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2f3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f3f OCA], [http://www.ebi.ac.uk/pdbsum/2f3f PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2f3f RCSB]</span> | ||
}} | }} | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Rondeau, J M.]] | [[Category: Rondeau, J M.]] | ||
| - | [[Category: AXF]] | ||
[[Category: alzheimer's disease]] | [[Category: alzheimer's disease]] | ||
[[Category: aspartic protease]] | [[Category: aspartic protease]] | ||
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[[Category: memapsin2]] | [[Category: memapsin2]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:57:22 2008'' |
Revision as of 23:57, 30 March 2008
| |||||||
| , resolution 2.300Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | BACE1, BACE (Homo sapiens) | ||||||
| Activity: | Memapsin 2, with EC number 3.4.23.46 | ||||||
| Related: | 2F3E
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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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