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PDBsum entry 1ive

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Hydrolase (o-glycosyl) PDB id
1ive
Jmol
Contents
Protein chains
388 a.a.
Ligands
NAG-NAG ×2
NAG-NAG-BMA-FUL
NAG-NAG-BMA
MAN-MAN
MAN
NAG-NDG ×2
NAG-NAG-BMA-FUC
NAG-NAG-BMA-MAN-
MAN-MAN
ST3 ×2
Metals
_CA ×2

References listed in PDB file
Key reference
Title Structures of aromatic inhibitors of influenza virus neuraminidase.
Authors M.J.Jedrzejas, S.Singh, W.J.Brouillette, W.G.Laver, G.M.Air, M.Luo.
Ref. Biochemistry, 1995, 34, 3144-3151. [DOI no: 10.1021/bi00010a003]
PubMed id 7880809
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.
Abstract
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.
Secondary reference #1
Title Structure-Based inhibitors of influenza virus sialidase. A benzoic acid lead with novel interaction.
Authors S.Singh, M.J.Jedrzejas, G.M.Air, M.Luo, W.G.Laver, W.J.Brouillette.
Ref. J Med Chem, 1995, 38, 3217-3225. [DOI no: 10.1021/jm00017a005]
PubMed id 7650674
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%.
Full text Abstract
Secondary reference #2
Title Benzoic acid inhibitors of influenza virus neuraminidase.
Authors M.Luo, M.J.Jedrzejas, S.Singh, C.L.White, W.J.Brouillette, G.M.Air, W.G.Laver.
Ref. Acta Crystallogr D Biol Crystallogr, 1995, 51, 504-510. [DOI no: 10.1107/S0907444994011698]
PubMed id 15299837
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.
Full text Abstract
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.
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.
The above figures are reproduced from the cited reference with permission from the IUCr
Secondary reference #3
Title Three-Dimensional structure of the neuraminidase of influenza virus a/tokyo/3/67 at 2.2 a resolution.
Authors J.N.Varghese, P.M.Colman.
Ref. J Mol Biol, 1991, 221, 473-486.
PubMed id 1920428
Abstract
PROCHECK
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