2QWG

THE X-RAY STRUCTURE OF A COMPLEX OF 5-N-ACETYL-4-AMINO-6-DIETHYLCARBOXAMIDE-4,5-DIHYDRO-2H-PYRAN-2-CARBOXYLIC ACID AND A DRUG RESISTANT VARIANT R292K OF TERN N9 INFLUENZA VIRUS NEURAMINIDASE

Summary for 2QWG

• Entry DOI: 10.2210/pdb2qwg/pdb
• Descriptor: NEURAMINIDASE, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: neuraminidase, influenza protein, drug resistant variant, sialic acid analogues, dana anologues, glycosylated protein, hydrolase, carboxamide derivatives
• Biological source: Influenza A virus
• Total number of polymer chains: 1
• Total formula weight: 45955.95

Authors

Varghese, J.N. (deposition date: 1998-04-07, release date: 1998-11-11, Last modification date: 2024-10-30)

Primary citation

Varghese, J.N.,Smith, P.W.,Sollis, S.L.,Blick, T.J.,Sahasrabudhe, A.,McKimm-Breschkin, J.L.,Colman, P.M.
Drug design against a shifting target: a structural basis for resistance to inhibitors in a variant of influenza virus neuraminidase.
Structure, 6:735-746, 1998

PubMed Abstract: Inhibitors of the influenza virus neuraminidase have been shown to be effective antiviral agents in humans. Several studies have reported the selection of novel influenza strains when the virus is cultured with neuraminidase inhibitors in vitro. These resistant viruses have mutations either in the neuraminidase or in the viral haemagglutinin. Inhibitors in which the glycerol sidechain at position 6 of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (Neu5Ac2en) has been replaced by carboxamide-linked hydrophobic substituents have recently been reported and shown to select neuraminidase variants. This study seeks to clarify the structural and functional consequences of replacing the glycerol sidechain of the inhibitor with other chemical constituents.

PubMed: 9655825
DOI: 10.1016/S0969-2126(98)00075-6

Experimental method

X-RAY DIFFRACTION (1.8 Å)