3O9K

Influenza NA in complex with compound 6

Summary for 3O9K

• Entry DOI: 10.2210/pdb3o9k/pdb
• Descriptor: Neuraminidase, 5-acetamido-2,6-anhydro-3,5-dideoxy-3-[(2E)-3-(4-methylphenyl)prop-2-en-1-yl]-D-glycero-D-galacto-non-2-enonic acid (2 entities in total)
• Functional Keywords: glycosidase, hydrolase
• Biological source: Influenza A virus (A/duck/Ukraine/1/1963(H3N8))
• Total number of polymer chains: 1
• Total formula weight: 43260.55

Authors

Russell, R.J.,Kerry, P.S. (deposition date: 2010-08-04, release date: 2010-12-15, Last modification date: 2020-07-29)

Primary citation

Rudrawar, S.,Dyason, J.C.,Rameix-Welti, M.A.,Rose, F.J.,Kerry, P.S.,Russell, R.J.,van der Werf, S.,Thomson, R.J.,Naffakh, N.,von Itzstein, M.
Novel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase.
Nat Commun, 1:113-113, 2010

PubMed Abstract: Influenza virus sialidase has an essential role in the virus' life cycle. Two distinct groups of influenza A virus sialidases have been established, that differ in the flexibility of the '150-loop', providing a more open active site in the apo form of the group-1 compared to group-2 enzymes. In this study we show, through a multidisciplinary approach, that novel sialic acid-based derivatives can exploit this structural difference and selectively inhibit the activity of group-1 sialidases. We also demonstrate that group-1 sialidases from drug-resistant mutant influenza viruses are sensitive to these designed compounds. Moreover, we have determined, by protein X-ray crystallography, that these inhibitors lock open the group-1 sialidase flexible 150-loop, in agreement with our molecular modelling prediction. This is the first direct proof that compounds may be developed to selectively target the pandemic A/H1N1, avian A/H5N1 and other group-1 sialidase-containing viruses, based on an open 150-loop conformation of the enzyme.

PubMed: 21081911
DOI: 10.1038/ncomms1114

Experimental method

X-RAY DIFFRACTION (2.4945 Å)