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PDBsum entry 2b8h
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References listed in PDB file
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Key reference
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Title
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Structure of a calcium-Deficient form of influenza virus neuraminidase: implications for substrate binding.
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Authors
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B.J.Smith,
T.Huyton,
R.P.Joosten,
J.L.Mckimm-Breschkin,
J.G.Zhang,
C.S.Luo,
M.Z.Lou,
N.E.Labrou,
T.P.Garrett.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2006,
62,
947-952.
[DOI no: ]
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PubMed id
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Abstract
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The X-ray structure of influenza virus neuraminidase (NA) isolated from whale,
subtype N9, has been determined at 2.2 A resolution and contains a tetrameric
protein in the asymmetric unit. In structures of NA determined previously, a
calcium ion is observed to coordinate amino acids near the substrate-binding
site. In three of the NA monomers determined here this calcium is absent,
resulting in structural alterations near the substrate-binding site. These
changes affect the conformation of residues that participate in several key
interactions between the enzyme and substrate and provide at a molecular level
the basis of the structural and functional role of calcium in substrate and
inhibitor binding. Several sulfate ions were identified in complex with the
protein. These are located in the active site, occupying the space reserved for
the substrate (sialic acid) carboxylate, and in positions leading away from the
substrate-binding site. These sites offer a new opportunity for the design of
inhibitors of influenza virus NA.
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Figure 1.
Figure 1 Ribbon diagram of the calcium-binding site and
structural changes between calcium-bound (green, chain A) and
calcium-free (cyan, chain B; pink, chain C; tan, chain D) forms
of NA. The loops L1 (245-251), L2 (295-298) and L3 (343-344)
adopt different conformations in the four monomers. In the
calcium-bound form, the protein backbone carbonyl O atoms of
Asp293, Gly297 and Asn347 and the side-chain carboxylate of
Asp324 all bind the calcium cation (yellow sphere). In the
calcium-free form of chain B, the carbonyl groups of Gly297 and
Asn347 are shown to be flipped from the conformation observed in
the calcium-bound form.
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The above figure is
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(2006,
62,
947-952)
copyright 2006.
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