3DUY
Crystal structure of human beta-secretase in complex with NVP-AFJ144
Summary for 3DUY
| Entry DOI | 10.2210/pdb3duy/pdb |
| Related | 3DV1 3DV5 |
| Descriptor | Beta-secretase 1, (2R,4S,5S)-N-butyl-4-hydroxy-2,7-dimethyl-5-{[N-(4-methylpentanoyl)-L-methionyl]amino}octanamide (3 entities in total) |
| Functional Keywords | beta-secretase, bace1, memapsin2, enzyme inhibitor complex, alzheimer's disease, alternative splicing, aspartyl protease, glycoprotein, hydrolase, membrane, protease, transmembrane, zymogen |
| Biological source | Homo sapiens |
| Cellular location | Membrane; Single-pass type I membrane protein: P56817 |
| Total number of polymer chains | 3 |
| Total formula weight | 135795.23 |
| Authors | Rondeau, J.-M. (deposition date: 2008-07-18, release date: 2009-02-24, Last modification date: 2024-11-06) |
| Primary citation | Machauer, R.,Veenstra, S.,Rondeau, J.M.,Tintelnot-Blomley, M.,Betschart, C.,Neumann, U.,Paganetti, P. Structure-based design and synthesis of macrocyclic peptidomimetic beta-secretase (BACE-1) inhibitors. Bioorg.Med.Chem.Lett., 19:1361-1365, 2009 Cited by PubMed Abstract: The hydroxyethylene octapeptide inhibitor OM99-2 served as starting point to create the tripeptide inhibitor 1 and its analogues 2a and b. An X-ray co-crystal structure of 1 with BACE-1 allowed the design and syntheses of a series of macrocyclic analogues 3a-h covalently linking the P1 and P3 side-chains. These inhibitors show improved enzymatic potency over their open-chain analogue. Inhibitor 3h also shows activity in a cellular system. PubMed: 19195886DOI: 10.1016/j.bmcl.2009.01.036 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.97 Å) |
Structure validation
Download full validation report
