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Literature summary for 3.2.1.18 extracted from

  • Lloren, K.K.S.; Kwon, J.J.; Choi, W.S.; Jeong, J.H.; Ahn, S.J.; Choi, Y.K.; Baek, Y.H.; Song, M.S.
    In vitro and in vivo characterization of novel neuraminidase substitutions in influenza A(H1N1)pdm09 virus identified using laninamivir-mediated in vitro selection (2019), J. Virol., 93, e01825-18.
    View publication on PubMedView publication on EuropePMC
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Cloned(Commentary)

Cloned (Comment) Organism
expressed in MDCK cells influenza A virus H1N1

Protein Variants

Protein Variants Comment Organism
D199E the mutant shows increased enzyme activity compared to the wild type enzyme influenza A virus H1N1
E119D the mutation confers reduced inhibition by oseltamivir (a 95-fold increase in the 50% inhibitory concentration) and highly reduced inhibition by zanamivir, peramivir. and laninamivir (2660fold, 460fold, and 651fold increases in the 50% inhibitory concentration, respectively) influenza A virus H1N1
E119G the mutation confers mainly reduced to highly reduced inhibition by zanamivir, peramivir, and laninamivir, but remains susceptible to oseltamivir influenza A virus H1N1
I321V the mutant shows normal inhibition by zanamivir, peramivir, laninamivir and oseltamivir compared to the wild type enzyme influenza A virus H1N1
K432E the mutant shows normal inhibition by zanamivir, peramivir, laninamivir and oseltamivir compared to the wild type enzyme influenza A virus H1N1
N200S the mutant shows normal inhibition by zanamivir, peramivir, laninamivir and oseltamivir compared to the wild type enzyme influenza A virus H1N1
N248D the mutant shows normal inhibition by zanamivir, peramivir, laninamivir and oseltamivir compared to the wild type enzyme influenza A virus H1N1
N270K the mutant shows normal inhibition by zanamivir, peramivir, laninamivir and oseltamivir compared to the wild type enzyme influenza A virus H1N1
N369K the mutant shows normal inhibition by zanamivir, peramivir, laninamivir and oseltamivir compared to the wild type enzyme influenza A virus H1N1
N386K the mutant shows normal inhibition by zanamivir, peramivir, laninamivir and oseltamivir compared to the wild type enzyme influenza A virus H1N1
P458T the mutant with decreased activity exhibits highly reduced inhibition by zanamivir, peramivir, laninamivir and oseltamivir compared to the wild type enzyme influenza A virus H1N1
Q136K the mutation confers mainly reduced to highly reduced inhibition by zanamivir, peramivir, and laninamivir, but remains susceptible to oseltamivir influenza A virus H1N1
R152K the mutant remains susceptible to peramivir, but confers reduced inhibition by zanamivir, oseltamivir, and laninamivir influenza A virus H1N1
V264I the mutant shows normal inhibition by zanamivir, peramivir, laninamivir and oseltamivir compared to the wild type enzyme influenza A virus H1N1

Inhibitors

Inhibitors Comment Organism Structure
laninamivir
-
 influenza A virus H1N1
oseltamivir
-
 influenza A virus H1N1
peramivir
-
 influenza A virus H1N1
zanamivir
-
 influenza A virus H1N1

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.049
-
 4-methylumbelliferyl alpha-D-N-acetylneuraminic acid wild type enzyme, at 37°C, pH not specified in the publication influenza A virus H1N1
0.2595
-
 4-methylumbelliferyl alpha-D-N-acetylneuraminic acid mutant enzyme D199E, at 37°C, pH not specified in the publication influenza A virus H1N1
0.6458
-
 4-methylumbelliferyl alpha-D-N-acetylneuraminic acid mutant enzyme P458T, at 37°C, pH not specified in the publication influenza A virus H1N1

Organism

Organism UniProt Comment Textmining
influenza A virus H1N1
-
 A/California/04/2009
-
influenza A virus H1N1 pdm09
-
 A/California/04/2009
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
4-methylumbelliferyl alpha-D-N-acetylneuraminic acid + H2O
-
 influenza A virus H1N1 4-methylumbelliferone + alpha-D-N-acetylneuraminic acid
-
 ?
4-methylumbelliferyl alpha-D-N-acetylneuraminic acid + H2O
-
 influenza A virus H1N1 pdm09 4-methylumbelliferone + alpha-D-N-acetylneuraminic acid
-
 ?

Synonyms

Synonyms Comment Organism
neuraminidase
-
 influenza A virus H1N1