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PDBsum entry 1ivc
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Hydrolase (o-glycosyl)
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PDB id
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1ivc
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References listed in PDB file
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Key reference
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Title
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Structures of aromatic inhibitors of influenza virus neuraminidase.
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Authors
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M.J.Jedrzejas,
S.Singh,
W.J.Brouillette,
W.G.Laver,
G.M.Air,
M.Luo.
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Ref.
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Biochemistry, 1995,
34,
3144-3151.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
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Abstract
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Neuraminidase (NA), a surface glycoprotein of influenza virus, is a potential
target for design of antiinfluenza agents. The crystal structure of influenza
virus neuraminidase showed that in the active site 11 residues are universally
conserved among all strains known so far. Several potent inhibitors based on the
carbohydrate compound 2-deoxy-2,3-didehydro-D-N-acetylneuraminic acid (DANA)
have been shown to bind to the conserved active site and to reduce virus
infection in animals when administered by nasal spray. Inhibitors of this type
are, however, rapidly excreted from physiological systems and may not be
effective in order to provide long-time protection. A new class of specific NA
inhibitors, which are benzoic acid derivatives, has been designed on the basis
of the three-dimensional structure of the NA-DANA complex and modeling of
derivatives of 4-(acetylamino)benzoic acid in the NA active site. Intermediates
were synthesized and were shown to moderately inhibit the NA activity and to
bind to the NA active site as predicted. These rudimentary inhibitors,
4-(acetylamino)-3-hydroxy-5-nitrobenzoic acid,
4-(acetylamino)-3-hydroxy-5-aminobenzoic acid, and
4-(acetylamino)-3-aminobenzoic acid, and their X-ray structures in complexes
with N2 (A/Tokyo/3/67) and B/Lee/40 neuraminidases have been analyzed. The
coordinates of such inhibitors complexed with NA were used as the starting model
for further design of more potent benzoic acid inhibitors. Because the active
site residues of NA are invariant, the designed aromatic inhibitors have the
potential to become an antiviral drug against all strains of influenza virus.
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Secondary reference #1
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Title
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Structure-Based inhibitors of influenza virus sialidase. A benzoic acid lead with novel interaction.
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Authors
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S.Singh,
M.J.Jedrzejas,
G.M.Air,
M.Luo,
W.G.Laver,
W.J.Brouillette.
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Ref.
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J Med Chem, 1995,
38,
3217-3225.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
90%.
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Secondary reference #2
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Title
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Benzoic acid inhibitors of influenza virus neuraminidase.
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Authors
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M.Luo,
M.J.Jedrzejas,
S.Singh,
C.L.White,
W.J.Brouillette,
G.M.Air,
W.G.Laver.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 1995,
51,
504-510.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
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Figure 3.
Fig. 3. A cartoon iagram of the
active site of A/Tokyo/3/67
N2 neuramiidase interacting
with sialic acid. Only he 11
universally conserved residues
are presented.
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Figure 4.
Fig. 4. The chemical structure
of three benzoic acid deriva-
tives, 4-(acetylamino)-3-amino
benzoic acid (BANA 108),
4-(acetylamino)-3-amino-5-
hydroxyl benzoic acd (BANA
106), and 4-(acetylamino)-3-
hydroxyl-5-nitro benzoic acid
(BANA 105). BANA stands
for benzoic acid inhibitor of
neuraminidase.
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The above figures are
reproduced from the cited reference
with permission from the IUCr
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Secondary reference #3
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Title
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Three-Dimensional structure of the neuraminidase of influenza virus a/tokyo/3/67 at 2.2 a resolution.
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Authors
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J.N.Varghese,
P.M.Colman.
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Ref.
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J Mol Biol, 1991,
221,
473-486.
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PubMed id
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