4TYD
Structure-based design of a novel series of azetidine inhibitors of the hepatitis C virus NS3/4A serine protease
Summary for 4TYD
| Entry DOI | 10.2210/pdb4tyd/pdb |
| Descriptor | NS3 protease, ZINC ION, (4R,6S,7Z,15S,17S)-17-[({7-methoxy-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinolin-4-yl}oxy)methyl]-13-methyl-N-[(1-methylcyclopropyl)sulfonyl]-2,14-dioxo-1,3,13-triazatricyclo[13.2.0.0~4,6~]heptadec-7-ene-4-carboxamide, ... (5 entities in total) |
| Functional Keywords | structure-based design, hcv ns3/4a serine protease, azetidine inhibitors, proteros biostructures gmbh, hydrolase |
| Biological source | Hepatitis C virus (isolate 1) |
| Total number of polymer chains | 12 |
| Total formula weight | 267727.95 |
| Authors | Parsy, C. (deposition date: 2014-07-08, release date: 2014-09-10, Last modification date: 2024-05-08) |
| Primary citation | Parsy, C.,Alexandre, F.R.,Brandt, G.,Caillet, C.,Cappelle, S.,Chaves, D.,Convard, T.,Derock, M.,Gloux, D.,Griffon, Y.,Lallos, L.,Leroy, F.,Liuzzi, M.,Loi, A.G.,Moulat, L.,Musiu, C.,Rahali, H.,Roques, V.,Seifer, M.,Standring, D.,Surleraux, D. Structure-based design of a novel series of azetidine inhibitors of the hepatitis C virus NS3/4A serine protease. Bioorg.Med.Chem.Lett., 24:4444-4449, 2014 Cited by PubMed Abstract: Structural homology between thrombin inhibitors and the early tetrapeptide HCV protease inhibitor led to the bioisosteric replacement of the P2 proline by a 2,4-disubstituted azetidine within the macrocyclic β-strand mimic. Molecular modeling guided the design of the series. This approach was validated by the excellent activity and selectivity in biochemical and cell based assays of this novel series and confirmed by the co-crystal structure of the inhibitor with the NS3/4A protein (PDB code: 4TYD). PubMed: 25155387DOI: 10.1016/j.bmcl.2014.08.002 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.84 Å) |
Structure validation
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