4GB1
Synthesis and Evaluation of Novel 3-C-alkylated-Neu5Ac2en Derivatives as Probes of Influenza Virus Sialidase 150-loop flexibility
Summary for 4GB1
| Entry DOI | 10.2210/pdb4gb1/pdb |
| Descriptor | Neuraminidase, 5-acetamido-2,6-anhydro-3,5-dideoxy-3-[(2E)-3-phenylprop-2-en-1-yl]-D-glycero-L-altro-non-2-enonic acid, CALCIUM ION, ... (4 entities in total) |
| Functional Keywords | enzyme, vial protein, glycosylation, hydrolase |
| Biological source | Influenza A virus |
| Total number of polymer chains | 1 |
| Total formula weight | 43662.06 |
| Authors | Kerry, P.S.,Rudrawar, S.,Rameix-Welti, M.-A.,Maggioni, A.,Dyason, J.C.,Rose, F.J.,van der Werf, S.,Thomson, R.J.,Naffakh, N.,Russell, R.J.M.,von Itzstein, M. (deposition date: 2012-07-26, release date: 2012-09-26, Last modification date: 2024-10-30) |
| Primary citation | Rudrawar, S.,Kerry, P.S.,Rameix-Welti, M.A.,Maggioni, A.,Dyason, J.C.,Rose, F.J.,van der Werf, S.,Thomson, R.J.,Naffakh, N.,Russell, R.J.,von Itzstein, M. Synthesis and evaluation of novel 3-C-alkylated-Neu5Ac2en derivatives as probes of influenza virus sialidase 150-loop flexibility. Org.Biomol.Chem., 10:8628-8639, 2012 Cited by PubMed Abstract: Novel 3-C-alkylated-Neu5Ac2en derivatives have been designed to target the expanded active site cavity of influenza virus sialidases with an open 150-loop, currently seen in X-ray crystal structures of influenza A virus group-1 (N1, N4, N5, N8), but not group-2 (N2, N9), sialidases. The compounds show selectivity for inhibition of H5N1 and pdm09 H1N1 sialidases over an N2 sialidase, providing evidence of the relative 150-loop flexibility of these sialidases. In a complex with N8 sialidase, the C3 substituent of 3-phenylally-Neu5Ac2en occupies the 150-cavity while the central ring and the remaining substituents bind the active site as seen for the unsubstituted template. This new class of inhibitors, which can 'trap' the open 150-loop form of the sialidase, should prove useful as probes of 150-loop flexibility. PubMed: 22976385DOI: 10.1039/c2ob25627d PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.62 Å) |
Structure validation
Download full validation report
