6HP0

Complex of Neuraminidase from H1N1 Influenza Virus in Complex with Oseltamivir Triazol Derivative

Summary for 6HP0

• Entry DOI: 10.2210/pdb6hp0/pdb
• Descriptor: Neuraminidase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (10 entities in total)
• Functional Keywords: neuraminidase, influenza, complex, inhibitor, viral protein
• Biological source: Influenza A virus (A/Texas/17/2009(H1N1))
• Total number of polymer chains: 4
• Total formula weight: 179477.47

Authors

Pachl, P.,Pokorna, J. (deposition date: 2018-09-19, release date: 2019-09-11, Last modification date: 2024-10-23)

Primary citation

Zima, V.,Albinana, C.B.,Rojikova, K.,Pokorna, J.,Pachl, P.,Rezacova, P.,Hudlicky, J.,Navratil, V.,Majer, P.,Konvalinka, J.,Kozisek, M.,Machara, A.
Investigation of flexibility of neuraminidase 150-loop using tamiflu derivatives in influenza A viruses H1N1 and H5N1.
Bioorg.Med.Chem., 27:2935-2947, 2019

PubMed Abstract: This study focuses on design, synthesis and in vitro evaluation of inhibitory potency of two series of sialylmimetic that target an exosite ("150-cavity") adjacent to the active site of influenza neuraminidases from A/California/07/2009 (H1N1) pandemic strain and A/chicken/Nakorn-Patom/Thailand/CU-K2-2004 (H5N1). The structure-activity analysis as well as 3-D structure of the complex of parental compound with the pandemic neuraminidase p09N1 revealed high flexibility of the 150-cavity towards various modification of the neuraminidase inhibitors. Furthermore, our comparison of two methods for inhibition constant determination performed at slightly different pH values suggest that the experimental conditions of the measurement could dramatically influence the outcome of the analysis in the compound-dependent manner. Therefore, previously reported K values determined at non-physiological pH should be carefully scrutinized.

PubMed: 31128993
DOI: 10.1016/j.bmc.2019.05.024

Experimental method

X-RAY DIFFRACTION (1.88 Å)