PDBsum entry 1inx

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Hydrolase PDB id
Protein chain
388 a.a.
NAG ×3
Waters ×237

References listed in PDB file
Key reference
Title A sialic acid-Derived phosphonate analog inhibits different strains of influenza virus neuraminidase with different efficiencies.
Authors C.L.White, M.N.Janakiraman, W.G.Laver, C.Philippon, A.Vasella, G.M.Air, M.Luo.
Ref. J Mol Biol, 1995, 245, 623-634.
PubMed id 7844831
A phosphonate analog of N-acetyl neuraminic acid (PANA) has been designed as a potential neuraminidase (NA) inhibitor and synthesized as both the alpha (ePANA) and beta (aPANA) anomers. Inhibition of type A (N2) and type B NA activity by ePANA was approximately a 100-fold better than by sialic acid, but inhibition of type A (N9) NA was only ten-fold better than by sialic acid. The aPANA compound was not a strong inhibitor for any of the NA strains tested. The crystal structures at 2.4 A resolution of ePANA complexed to type A (N2) NA, type A (N9) NA and type B NA and aPANA complexed to type A (N2) NA showed that neither of the PANA compounds distorted the NA active site upon binding. No significant differences in the NA-ePANA complex structures were found to explain the anomalous inhibition of N9 neuraminidase by ePANA. We put forward the hypothesis that an increase in the ePANA inhibition compared to that caused by sialic acid is due to (1) a stronger electrostatic interaction between the inhibitor phosphonyl group and the active site arginine pocket and (2) a lower distortion energy requirement for binding of ePANA.
Secondary reference #1
Title Structure of influenza virus neuraminidase b/lee/40 complexed with sialic acid and a dehydro analog at 1.8-A resolution: implications for the catalytic mechanism.
Authors M.N.Janakiraman, C.L.White, W.G.Laver, G.M.Air, M.Luo.
Ref. Biochemistry, 1994, 33, 8172-8179. [DOI no: 10.1021/bi00193a002]
PubMed id 8031750
Full text Abstract
Secondary reference #2
Title Three-Dimensional structure of the neuraminidase of influenza virus a/tokyo/3/67 at 2.2 a resolution.
Authors J.N.Varghese, P.M.Colman.
Ref. J Mol Biol, 1991, 221, 473-486.
PubMed id 1920428
Secondary reference #3
Title Refined atomic structures of n9 subtype influenza virus neuraminidase and escape mutants.
Authors W.R.Tulip, J.N.Varghese, A.T.Baker, A.Van donkelaar, W.G.Laver, R.G.Webster, P.M.Colman.
Ref. J Mol Biol, 1991, 221, 487-497.
PubMed id 1920429
Secondary reference #4
Title Phosphonic-Acid analogs of the n-Acetyl-2-Deoxyneuraminic acids: synthesis and inhibition of vibrio choleae sialidase
Authors K.Walliman, A.Vasella.
Ref. helv chim acta, 1990, 73, 1359.
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