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Title
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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.
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Authors
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M.N.Janakiraman,
C.L.White,
W.G.Laver,
G.M.Air,
M.Luo.
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Ref.
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Biochemistry, 1994,
33,
8172-8179.
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PubMed id
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Abstract
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Neuraminidase is one of the two glycoprotein spikes protruding from the
influenza virus membrane. We have determined by X-ray crystallography the native
structure of B/Lee/40 neuraminidase (NA) and the structures of its crystals
soaked with a substrate, N-acetylneuraminyllactose (NANL), and an inhibitor,
2-deoxy-2,3-didehydro-N-acetylneuraminic acid (DANA) at 1.8-A resolution. NANL
was hydrolyzed by the crystalline NA to generate the product N-acetylneuraminic
acid (NANA, also known as sialic acid), which is still able to bind to NA. In
the difference Fourier map of the presumed NA-NANA complex, the moiety bound in
the active site had a distorted boat conformation of NANA, but there is no
significant electron density for O2. The structure of the bound moiety is not
identical to that of chemically synthesized DANA soaked into NA crystals.
Prolonged incubation of NANA with NA in solution at room temperature produced
only a trace amount of DANA as detected by NMR. On the basis of our studies, a
mechanism is proposed for the enzymatic hydrolysis by influenza virus
neuraminidase.
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