2OHQ
X-ray crystal structure of beta secretase complexed with compound 4
Summary for 2OHQ
| Entry DOI | 10.2210/pdb2ohq/pdb |
| Related | 2OF0 2OHK 2OHL 2OHM 2OHN 2OHP 2OHR 2OHS 2OHT 2OHU |
| Descriptor | Beta-secretase 1, IODIDE ION, DIMETHYL SULFOXIDE, ... (6 entities in total) |
| Functional Keywords | alzheimer's disease, aspartic protease, aspartyl protease, base, beta-secretase, glycoprotein, hydrolase, memapsin 2, transmembrane, zymogen |
| Biological source | Homo sapiens (human) |
| Cellular location | Membrane; Single-pass type I membrane protein: P56817 |
| Total number of polymer chains | 1 |
| Total formula weight | 45569.82 |
| Authors | Patel, S. (deposition date: 2007-01-10, release date: 2007-03-13, Last modification date: 2024-11-13) |
| Primary citation | Congreve, M.,Aharony, D.,Albert, J.,Callaghan, O.,Campbell, J.,Carr, R.A.,Chessari, G.,Cowan, S.,Edwards, P.D.,Frederickson, M.,McMenamin, R.,Murray, C.W.,Patel, S.,Wallis, N. Application of fragment screening by X-ray crystallography to the discovery of aminopyridines as inhibitors of beta-secretase. J.Med.Chem., 50:1124-1132, 2007 Cited by PubMed Abstract: Fragment-based lead discovery has been successfully applied to the aspartyl protease enzyme beta-secretase (BACE-1). Fragment hits that contained an aminopyridine motif binding to the two catalytic aspartic acid residues in the active site of the enzyme were the chemical starting points. Structure-based design approaches have led to identification of low micromolar lead compounds that retain these interactions and additionally occupy adjacent hydrophobic pockets of the active site. These leads form two subseries, for which compounds 4 (IC50 = 25 microM) and 6c (IC50 = 24 microM) are representative. In the latter series, further optimization has led to 8a (IC50 = 690 nM). PubMed: 17315857DOI: 10.1021/jm061197u PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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