1DXW
structure of hetero complex of non structural protein (NS) of hepatitis C virus (HCV) and synthetic peptidic compound
Summary for 1DXW
| Entry DOI | 10.2210/pdb1dxw/pdb |
| Related | 1BT7 |
| NMR Information | BMRB: 4617 |
| Related PRD ID | PRD_000426 |
| Descriptor | SERINE PROTEASE, N-(tert-butoxycarbonyl)-L-alpha-glutamyl-N-[(1R)-1-(carboxycarbonyl)-3,3-difluoropropyl]-L-leucinamide, ZINC ION (3 entities in total) |
| Functional Keywords | non structural protein, hepatitis c virus, serine protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | HEPATITIS C VIRUS (HCV) |
| Total number of polymer chains | 1 |
| Total formula weight | 20209.44 |
| Authors | Barbato, G.,Cicero, D.O.,Cordier, F.,Narjes, F.,Gerlach, B.,Sambucini, S.,Grzesiek, S.,Matassa, V.G.,Defrancesco, R.,Bazzo, R. (deposition date: 2000-01-17, release date: 2001-01-12, Last modification date: 2024-11-13) |
| Primary citation | Barbato, G.,Cicero, D.O.,Cordier, F.,Narjes, F.,Gerlach, B.,Sambucini, S.,Grzesiek, S.,Matassa, V.G.,Defrancesco, R.,Bazzo, R. Inhibitor Binding Induces Active Site Stabilisation of the Hcv Ns3 Protein Serine Protease Domain Embo J., 19:1195-, 2000 Cited by PubMed Abstract: Few structures of viral serine proteases, those encoded by the Sindbis and Semliki Forest viruses, hepatitis C virus (HCV) and cytomegalovirus, have been reported. In the life cycle of HCV a crucial role is played by a chymotrypsin-like serine protease encoded at the N-terminus of the viral NS3 protein, the solution structure of which we present here complexed with a covalently bound reversible inhibitor. Unexpectedly, the residue in the P2 position of the inhibitor induces an effective stabilization of the catalytic His-Asp hydrogen bond, by shielding that region of the protease from the solvent. This interaction appears crucial in the activation of the enzyme catalytic machinery and represents an unprecedented observation for this family of enzymes. Our data suggest that natural substrates of this serine protease could contribute to the enzyme activation by a similar induced-fit mechanism. The high degree of similarity at the His-Asp catalytic site region between HCV NS3 and other viral serine proteases suggests that this behaviour could be a more general feature for this category of viral enzymes. PubMed: 10716920DOI: 10.1093/EMBOJ/19.6.1195 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
