6EKS
Vibrio cholerae neuraminidase complexed with oseltamivir carboxylate
Summary for 6EKS
| Entry DOI | 10.2210/pdb6eks/pdb |
| Descriptor | Sialidase, CALCIUM ION, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | sialidase, bacterial protein, infection, hydrolase |
| Biological source | Vibrio cholerae serotype O1 |
| Cellular location | Secreted: P0C6E9 |
| Total number of polymer chains | 1 |
| Total formula weight | 83760.42 |
| Authors | Schuetz, A.,Heinemann, U. (deposition date: 2017-09-27, release date: 2017-11-29, Last modification date: 2024-01-17) |
| Primary citation | Quosdorf, S.,Schuetz, A.,Kolodziej, H. Different Inhibitory Potencies of Oseltamivir Carboxylate, Zanamivir, and Several Tannins on Bacterial and Viral Neuraminidases as Assessed in a Cell-Free Fluorescence-Based Enzyme Inhibition Assay. Molecules, 22:-, 2017 Cited by PubMed Abstract: Neuraminidaseis a key enzyme in the life cycle of influenza viruses and is present in some bacterial pathogens. We here assess the inhibitory potency of plant tannins versus clinically used inhibitors on both a viral and a bacterial model neuraminidase by applying the 2'-(4-methylumbelliferyl)-α-d--acetylneuraminic acid (MUNANA)-based activity assay. A range of flavan-3-ols, ellagitannins and chemically defined proanthocyanidin fractions was evaluated in comparison to oseltamivir carboxylate and zanamivir for their inhibitory activities against viral influenza A (H1N1) and bacterial neuraminidase (VCNA). Compared to the positive controls, all tested polyphenols displayed a weak inhibition of the viral enzyme but similar or even higher potency on the bacterial neuraminidase. Structure-activity relationship analyses revealed the presence of galloyl groups and the hydroxylation pattern of the flavan skeleton to be crucial for inhibitory activity. The combination of zanamivir and EPs 7630 (root extract of ) showed synergistic inhibitory effects on the bacterial neuraminidase. Co-crystal structures of VCNA with oseltamivir carboxylate and zanamivir provided insight into bacterial versus viral enzyme-inhibitor interactions. The current data clearly indicate that inhibitor potency strongly depends on the biological origin of the enzyme and that results are not readily transferable. The therapeutic relevance of our findings is briefly discussed. PubMed: 29149072DOI: 10.3390/molecules22111989 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.87 Å) |
Structure validation
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