On the lower susceptibility of oseltamivir to influenza neuraminidase subtype N1 than those in N2 and N9.

ABSTRACT: Aiming to understand, at the molecular level, why oseltamivir (OTV) cannot be used for inhibition of human influenza neuraminidase subtype N1 as effectively as for subtypes N2 and N9, molecular dynamics simulations were carried out for the three complexes, OTV-N1, OTV-N2, and OTV-N9. The three-dimensional OTV-N2 and OTV-N9 initial structures were represented by the x-ray structures, whereas that of OTV-N1, whose x-ray structure is not yet solved, was built up using the aligned sequence of H5N1 isolated from humans in Thailand with the x-ray structure of the N2-substrate as the template. In comparison to the OTV-N2 and OTV-N9 complexes, dramatic changes were observed in the OTV conformation in the OTV-N1 complex in which two of its bulky side chains, N-acethyl (-NHAc) and 1-ethylproxy group

SUBMITTER: Aruksakunwong O 

PROVIDER: S-EPMC1779986 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature