1INF

INFLUENZA VIRUS B/LEE/40 NEURAMINIDASE COMPLEXED WITH BANA113 INHIBITOR

Summary for 1INF

• Entry DOI: 10.2210/pdb1inf/pdb
• Descriptor: INFLUENZA VIRUS B/LEE/40 NEURAMINIDASE, 2-acetamido-2-deoxy-beta-D-glucopyranose, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: neuraminidase, sialidase, hydrolase, o-glycosyl, hydrolase (o-glycosyl)
• Biological source: Influenza B virus
• Cellular location: Virion membrane (By similarity): P03474
• Total number of polymer chains: 1
• Total formula weight: 43971.94

Authors

Jedrzejas, M.J.,Luo, M. (deposition date: 1995-07-07, release date: 1996-08-17, Last modification date: 2020-07-29)

Primary citation

Singh, S.,Jedrzejas, M.J.,Air, G.M.,Luo, M.,Laver, W.G.,Brouillette, W.J.
Structure-based inhibitors of influenza virus sialidase. A benzoic acid lead with novel interaction.
J.Med.Chem., 38:3217-3225, 1995

PubMed 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.

PubMed: 7650674
DOI: 10.1021/jm00017a005

Experimental method

X-RAY DIFFRACTION (2.4 Å)