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Literature summary extracted from

  • Collins, P.J.; Haire, L.F.; Lin, Y.P.; Liu, J.; Russell, R.J.; Walker, P.A.; Skehel, J.J.; Martin, S.R.; Hay, A.J.; Gamblin, S.J.
    Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutants (2008), Nature, 453, 1258-1261.
    View publication on PubMed

Application

EC Number Application Comment Organism
3.2.1.18 medicine isolation of mutants from H5N1-infected patients to explain the molecular basis of resistance to oseltamivir. Mutants are resistant to oseltamivir but still strongly inhibited by zanamivir owing to an altered hydrophobic pocket in the active site of the enzyme required for oseltamivir binding unidentified influenza virus

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
3.2.1.18 wild-type and mutants H274Y, N294S, Y252H in complex with oseltamivir. Mutants are resistant to oseltamivir but still strongly inhibited by zanamivir owing to an altered hydrophobic pocket in the active site of the enzyme required for oseltamivir binding unidentified influenza virus

Protein Variants

EC Number Protein Variants Comment Organism
3.2.1.18 H274Y mutant isolated from patient infected with H5N1. Ratio Ki mutant/Ki wild-type for inhibition by oseltamivir is 265, for inhibition by zanamivir is 1.9, respectively unidentified influenza virus
3.2.1.18 N294S mutant isolated from patient infected with H5N1. Ratio Ki mutant/Ki wild-type for inhibition by oseltamivir is 81, for inhibition by zanamivir is 7.2, respectively unidentified influenza virus
3.2.1.18 Y252H mutant isolated from patient infected with H5N1. Ratio Ki mutant/Ki wild-type for inhibition by oseltamivir is 0.1, for inhibition by zanamivir is 1.2, respectively unidentified influenza virus

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.2.1.18 oseltamivir
-
 unidentified influenza virus
3.2.1.18 zanamivir
-
 unidentified influenza virus

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
3.2.1.18 0.0063
-
 2-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid wild-type unidentified influenza virus
3.2.1.18 0.0075
-
 2-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid mutant Y252H unidentified influenza virus
3.2.1.18 0.027
-
 2-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid mutant H274Y unidentified influenza virus
3.2.1.18 0.053
-
 2-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid mutant N294S unidentified influenza virus

Organism

EC Number Organism UniProt Comment Textmining
3.2.1.18 unidentified influenza virus
-
 type H5N1
-
3.2.1.18 unidentified influenza virus H5N1
-
 type H5N1
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.2.1.18 2-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid + H2O
-
 unidentified influenza virus 4-methylumbelliferone + N-acetylneuraminic acid
-
 ?
3.2.1.18 2-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid + H2O
-
 unidentified influenza virus H5N1 4-methylumbelliferone + N-acetylneuraminic acid
-
 ?

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
3.2.1.18 0.0000001
-
 zanamivir wild-type unidentified influenza virus
3.2.1.18 0.00000032
-
 oseltamivir wild-type unidentified influenza virus