1b9s: Difference between revisions
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[[Image:1b9s.gif|left|200px]] | [[Image:1b9s.gif|left|200px]] | ||
'''NOVEL AROMATIC INHIBITORS OF INFLUENZA VIRUS NEURAMINIDASE MAKE SELECTIVE INTERACTIONS WITH CONSERVED RESIDUES AND WATER MOLECULES IN THE ACTIVE SITE''' | {{Structure | ||
|PDB= 1b9s |SIZE=350|CAPTION= <scene name='initialview01'>1b9s</scene>, resolution 2.5Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> and <scene name='pdbligand=FDI:4-(N-ACETYLAMINO)-3-[N-(2-ETHYLBUTANOYLAMINO)]BENZOIC ACID'>FDI</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Exo-alpha-sialidase Exo-alpha-sialidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.18 3.2.1.18] | |||
|GENE= | |||
}} | |||
'''NOVEL AROMATIC INHIBITORS OF INFLUENZA VIRUS NEURAMINIDASE MAKE SELECTIVE INTERACTIONS WITH CONSERVED RESIDUES AND WATER MOLECULES IN THE ACTIVE SITE''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1B9S is a [ | 1B9S is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Influenza_b_virus Influenza b virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B9S OCA]. | ||
==Reference== | ==Reference== | ||
Novel aromatic inhibitors of influenza virus neuraminidase make selective interactions with conserved residues and water molecules in the active site., Finley JB, Atigadda VR, Duarte F, Zhao JJ, Brouillette WJ, Air GM, Luo M, J Mol Biol. 1999 Nov 12;293(5):1107-19. PMID:[http:// | Novel aromatic inhibitors of influenza virus neuraminidase make selective interactions with conserved residues and water molecules in the active site., Finley JB, Atigadda VR, Duarte F, Zhao JJ, Brouillette WJ, Air GM, Luo M, J Mol Biol. 1999 Nov 12;293(5):1107-19. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10547289 10547289] | ||
[[Category: Exo-alpha-sialidase]] | [[Category: Exo-alpha-sialidase]] | ||
[[Category: Influenza b virus]] | [[Category: Influenza b virus]] | ||
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[[Category: sialidase]] | [[Category: sialidase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:08:07 2008'' | ||
Revision as of 11:08, 20 March 2008
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| , resolution 2.5Å | |||||||
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| Ligands: | , and | ||||||
| Activity: | Exo-alpha-sialidase, with EC number 3.2.1.18 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
NOVEL AROMATIC INHIBITORS OF INFLUENZA VIRUS NEURAMINIDASE MAKE SELECTIVE INTERACTIONS WITH CONSERVED RESIDUES AND WATER MOLECULES IN THE ACTIVE SITE
OverviewOverview
The active site of type A or B influenza virus neuraminidase is composed of 11 conserved residues that directly interact with the substrate, sialic acid. An aromatic benzene ring has been used to replace the pyranose of sialic acid in our design of novel neuraminidase inhibitors. A bis(hydroxymethyl)pyrrolidinone ring was constructed in place of the N-acetyl group on the sialic acid. The hydroxymethyl groups replace two active site water molecules, which resulted in the high affinity of the nanomolar inhibitors. However, these inhibitors have greater potency for type A influenza virus than for type B influenza virus. To resolve the differences, we determined the X-ray crystal structure of three benzoic acid substituted inhibitors bound to the active site of B/Lee/40 neuraminidase. The investigation of a hydrophobic aliphatic group and a hydrophilic guanidino group on the aromatic inhibitors shows changes in the interaction with the active site residue Glu275. The results provide an explanation for the difference in efficacy of these inhibitors against types A and B viruses, even though the 11 active site residues of the neuraminidase are conserved.
About this StructureAbout this Structure
1B9S is a Single protein structure of sequence from Influenza b virus. Full crystallographic information is available from OCA.
ReferenceReference
Novel aromatic inhibitors of influenza virus neuraminidase make selective interactions with conserved residues and water molecules in the active site., Finley JB, Atigadda VR, Duarte F, Zhao JJ, Brouillette WJ, Air GM, Luo M, J Mol Biol. 1999 Nov 12;293(5):1107-19. PMID:10547289
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