Literature summary for 3.2.1.18 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.

Search for more literature for 3.2.1.18

Application

Application	Comment	Organism
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)

Crystallization (Comment)	Organism
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

Protein Variants	Comment	Organism
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
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
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

Inhibitors	Comment	Organism	Structure
oseltamivir	-	unidentified influenza virus
zanamivir	-	unidentified influenza virus

KM Value [mM]

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

Organism

Organism	UniProt	Comment	Textmining
unidentified influenza virus	-	type H5N1	-
unidentified influenza virus H5N1	-	type H5N1	-

Substrates and Products (Substrate)

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

Ki Value [mM]

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

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Release 2023.1 (January 2023)