2fdp
From Proteopedia
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=FRP:N1-((2S,3S,5R)-3-AMINO-6-(4-FLUOROPHENYLAMINO)-5-METHYL-6-OXO-1-PHENYLHEXAN-2-YL)-N3,N3-DIPROPYLISOPHTHALAMIDE'>FRP</scene> | |LIGAND= <scene name='pdbligand=FRP:N1-((2S,3S,5R)-3-AMINO-6-(4-FLUOROPHENYLAMINO)-5-METHYL-6-OXO-1-PHENYLHEXAN-2-YL)-N3,N3-DIPROPYLISOPHTHALAMIDE'>FRP</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 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= BACE1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fdp OCA], [http://www.ebi.ac.uk/pdbsum/2fdp PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fdp RCSB]</span> | ||
}} | }} | ||
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[[Category: Yang, W.]] | [[Category: Yang, W.]] | ||
[[Category: Zhong, M.]] | [[Category: Zhong, M.]] | ||
| - | [[Category: FRP]] | ||
[[Category: aspartyl protease]] | [[Category: aspartyl protease]] | ||
[[Category: bace]] | [[Category: bace]] | ||
| - | ''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 03:01:21 2008'' |
Revision as of 00:01, 31 March 2008
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| , resolution 2.500Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | BACE1 (Homo sapiens) | ||||||
| Activity: | Memapsin 2, with EC number 3.4.23.46 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of beta-secretase complexed with an amino-ethylene inhibitor
Overview
A series of novel beta-site amyloid precursor protein cleaving enzyme (BACE-1) inhibitors containing an aminoethylene (AE) tetrahedral intermediate isostere were synthesized and evaluated in comparison to corresponding hydroxyethylene (HE) compounds. Enzymatic inhibitory values were similar for both isosteres, as were structure-activity relationships with respect to stereochemical preference and substituent variation (P2/P3, P1, and P2'); however, the AE compounds were markedly more potent in a cell-based assay for reduction of beta-secretase activity. The incorporation of preferred P2/P3, P1, and P2' substituents into the AE pharmacophore yielded compound 7, which possessed enzymatic and cell assay IC(50)s of 26 nM and 180 nM, respectively. A three-dimensional crystal structure of 7 in complex with BACE-1 revealed that the amino group of the inhibitor core engages the catalytic aspartates in a manner analogous to hydroxyl groups in HE inhibitors. The AE isostere class represents a promising advance in the development of BACE-1 inhibitors.
About this Structure
2FDP is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Aminoethylenes: a tetrahedral intermediate isostere yielding potent inhibitors of the aspartyl protease BACE-1., Yang W, Lu W, Lu Y, Zhong M, Sun J, Thomas AE, Wilkinson JM, Fucini RV, Lam M, Randal M, Shi XP, Jacobs JW, McDowell RS, Gordon EM, Ballinger MD, J Med Chem. 2006 Feb 9;49(3):839-42. PMID:16451048
Page seeded by OCA on Mon Mar 31 03:01:21 2008
Categories: Homo sapiens | Memapsin 2 | Single protein | Ballinger, M D. | Fucini, R V. | Gordon, E M. | Jacobs, J W. | Lam, M. | Lu, W. | Lu, Y. | McDowell, R S. | Randal, M. | Shi, X P. | Sun, J. | Thomas, A E. | Wilkinson, J M. | Yang, W. | Zhong, M. | Aspartyl protease | Bace
