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PDBsum entry 1inh

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Hydrolase (o-glycosyl) PDB id
1inh
Jmol
Contents
Protein chains
388 a.a. *
Ligands
NAG-NAG ×4
NAG-NAG-BMA-FUL
NAG-MAN ×2
BMA-MAN-BMA
NAG-NAG-BMA-FUC
NAG
NAG-BMA-MAN-MAN
ST6 ×2
Metals
_CA ×2
* Residue conservation analysis

References listed in PDB file
Key reference
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
Abstract
Influenza virus sialidase is a surface enzyme that is essential for infection of the virus. The catalytic site is highly conserved among all known influenza variants, suggesting that this protein is a suitable target for drug intervention. The most potent known inhibitors are analogs of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en), particularly the 4-guanidino derivative (4-guanidino-Neu5Ac2en). We utilized the benzene ring of 4-(N-acetylamino)benzoic acids as a cyclic template to substitute for the dihydropyran ring of Neu5Ac2en. In this study several 3-(N-acylamino) derivatives were prepared as potential replacements for the glycerol side chain of Neu5Ac2en, and some were found to interact with the same binding subsite of sialidase. Of greater significance was the observation that the 3-guanidinobenzoic acid derivative (equivalent to the 4-guanidino grouping of 4-guanidino-Neu5Ac2en), the most potent benzoic acid inhibitor of influenza sialidase thus far identified (IC50 = 10 microM), occupied the glycerol-binding subsite on sialidase as opposed to the guanidino-binding subsite. This benzoic acid derivative thus provides a new compound that interacts in a novel manner with the catalytic site of influenza sialidase.
Secondary reference #1
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
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 #2
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
Full text Abstract
Secondary reference #3
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
Full text Abstract
Secondary reference #4
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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